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Official websites use. Share sensitive information only on official, secure websites. E-mail: pietro. Funding: This study was supported by an independent grant n. At any time, height z -score decrease in the ATX group was higher than the corresponding decrease observed in the MPH group, but the difference was significantly relevant only during the first year of treatment. However, using Tanner's percentile, a subset of patients showed a degree of growth lower than expected. We conclude that ADHD drugs show a negative effect on linear growth in children in middle term. Atomoxetine ATX , a selective norepinephrine reuptake inhibitor, is considered as a second choice Cheng et al. Adverse events may occur both with psychostimulants and ATX. Available evidence suggests that children and adolescents are at higher risk than adults for adverse events during treatment with psychotropic drugs Greenhill et al. According to a systematic review Faraone et al. The effect, although attenuated, persisted over time for 4 years Mattes and Gittelman However, discontinuation of treatment with stimulants showed a compensatory growth spurt Mattes and Gittelman ; Klein et al. Two additional meta-analyses assessed reported the effect of long-term use of ATX on height and weight. The first showed a decrease in weight average 2. The second meta-analysis reported a less evident effect on weight and height, 0. Care providers choose the treatment based on their own experience, and on current clinical practice. Italian law requires close monitoring of drugs for 2 years after registration, in order to assess safety in current clinical practice. An observational post-marketing study of pharmacovigilance is mandatory for every new drug approved for ADHD. This observational prospective study included children and adolescents 6—18 years of age with ADHD, who were consecutively recruited from 87 centers accredited for the management of ADHD in Italy between June and June Participants were either referred by their child neuropsychiatrists or self-referred to a reference center for a suspicion of ADHD. Accordingly, to be diagnosed with ADHD, subjects had to present with a significant functional impairment and symptoms had to: 1 Be present, at least in part, before the age of 7 years, 2 persist for at least 6 months, and 3 be present in more than one setting e. All subjects were screened for other mental disorders, and participants with an autism spectrum disorder were excluded, as per DSM-IV criteria. Subjects with follow-up or compliance problems were also excluded. All subjects who accepted the pharmacological treatment signed an informed consent explaining the aim of the study and the tests to be performed in order to evaluate the primary parameters i. Two study groups were defined according to the pharmacological treatment, and the choice of treatment was based on current clinical practice by child neuropsychiatrists. This group consisted of subjects treated with MPH plus behavioral treatment. MPH was administered orally 0. A methylphenidate test dose of 0. The dosage could be increased up to 0. The duration of the renewable prescription was 1 month. This group consisted of subjects treated with ATX plus behavioral treatment. Route of administration was oral, with the following schedule: Beginning with 0. Duration of the renewable prescription was 1 month. All relevant information was collected by standard procedures. The clinical assessment was performed monthly, and included measurement of height in centimeters, and of weight in kilograms. Height and weight measurements were collected in according Tanner's standard procedure Tanner et al. Each measure of weight and height was also computed in percentiles. Clinical monitoring of the register included regular checking via the Internet. Centers, child psychiatrist services, and pediatricians could access this restricted area through user i. The required sample size was estimated with respect to the 1 year variation in height z -score the primary outcome of the study , based on the paired Student's t test comparison of the mean value between baseline and 12 months within the treatment group , two tailed we were interested in demonstrating differences in height z -score variation in whatever direction. From previous studies, the standard deviation of the 1 year variation in height z -score in the overall group of subjects, apart from sex and age, was estimated at 0. Categorical variables i. In order to maximize the number of subjects included in the statistical analyses, data were separately analyzed according to three reference periods: From enrollment time 0 to 6 months, from 0 to 12 months, and from 0 to 24 months of follow-up. The last two groups were excluded from the analysis Fig. Flow chart of patients at 6 months of follow-up. The figure reports the number of patients included in weight and height analysis, stratified for each group of treatment methylphenidate group, atomoxetine group. The reasons for which the patients were excluded from analysis were also reported. For any reference period, only subjects with data at baseline and at the end of the period were included in the statistical analyses. Subsequently, each subject was classified as passing to a lower percentile percentile decreased , remaining in the same percentile percentile unchanged , or passing to a higher percentile percentile increased from baseline to the end of the reference period. The frequency of subjects shifting to a lower percentile class was compared with that of those moving to a higher class using the binomial test. To take into account the effect of sex and age, height was also transformed in z -score, according to the formula. Because of asymmetry in the variable distribution, weight could not be transformed in z -scores, and, therefore, was analyzed and presented as raw data. Comparisons within the MPH or ATX groups with respect to height and weight data were performed by paired Student's t test to compare measurements taken at baseline and at the end of the specific reference period within each treatment group. The differences between the MPH and ATX groups for height and weight changes, occurring during the period, were tested using Student's t test for independent samples. Nonparametric tests Wilcoxon and Mann—Whitney U tests for paired data and independent samples, respectively were also performed on weight data to validate results of parametric tests. As the results were concordant, only parametric tests were reported. Of these, Stratified by type of treatment, MPH was prescribed at average daily dose equal to 0. ATX was prescribed at average daily dose of No significant differences were found between MPH and ATX groups, except for sex when comparing the two groups of treatment in relation to the period 0 versus 24 months, when a lower proportion of females was observed in the ATX group 46 males and 9 females in the MPH group vs. During the study, monitoring of height and weight was recommended monthly. The mean number of height measures per subject was 6. For primary analysis, we used follow-up data at 6, 12, and 24 months. One thousand and sixty-four Reasons for dropping out are reported in Figure 1. Five hundred and ninety subjects were included in the analysis Table 1. The comparison for age, sex, subtype of ADHD and comorbidity showed no significant differences between the subjects included in the analysis and those excluded, except for the depression. Two hundred and ninety-six out of Percentile variations are shown in Table 2. As can be seen, in all reference periods, the proportion of subjects shifting to a lower percentile class was larger than that of those moving to a higher percentile class. The difference between these two groups has always been significant, except for MPH subjects in the reference period 0—24 months. The difference was stronger in ATX- than in MPH-treated subjects; however, the difference between the two groups was significant only for the reference periods 0—6 months and 0—12 months. The binomial test refers to the comparison between frequencies of percentile decreased and increased subjects, based on the null hypothesis of equal distribution between the two categories. We calculated the mean value of weight before the treatment and after 6, 12, and 24 months. For MPH, at each time point, a statistically significant weight increase was detected. Similarly, a statistically significant difference was observed for ATX. These findings are summarized in Table 3. Unpaired Student's t test: Comparisons between MPH- and ATX-treated subjects regarding weight changes between baseline and the end of the specific reference period. Paired Student's t test: Comparisons between measurements taken at baseline and at the end of the specific reference period, within each treatment group. Five hundred and seventy-four subjects were included in the analyses Table 4. The comparison for age, sex, subtype of ADHD, and comorbidity between the group included in the analysis and the one excluded, showed a statistically significant difference only for anxiety. Two hundred and eighty-eight out of Percentile variations are shown in Table 5. The proportion of subjects shifting to a lower percentile class was higher than that of those moving to a higher percentile class, but the difference was significant only for ATX subjects in the reference periods 0—12 months and 0—24 months. The difference was slightly stronger in ATX- than in MPH-treated subjects; however, the difference between the two groups never reached statistical significance. We analyzed the mean value of height before the treatment and after 6, 12, and 24 months Table 6. A statistically significant increase of height was detected in the MPH group. Unpaired Student's t test: Comparisons between MPH and ATX-treated subjects regarding weight changes between baseline and the end of the specific reference period. The results are summarized in Table 7. The study showed a different growth rate between the two drugs, with ATX-treated patients growing significantly more slowly than MPH-treated patients. With regard to weight, there was a significant trend for weight increase for both drugs. For the effect on height we observed a statistically significant decrease, evaluated in percentiles, for both drugs. However, comparing the effect between the two drugs on height decrease, a statistically significant difference were observed only at 12 months. Although the two variables, weight and height, are both important in the assessment of growth, height is more important because, once growth stops at the end of adolescence, height cannot increase any more, whereas weight changes throughout life. Therefore, in order to more accurately assess growth with respect to height, we used the z -score that correlates with chronological age and gender. The z -score values after 12 and 24 months of therapy were more reduced in the ATX group than in the MPH one, but a significant difference was detected only at 12 months. At 24 months of follow-up, a greater difference in z -score between the two groups was observed, but it is not statistically significant, because the number of subjects included in this subanalysis, in the two groups, was lower. Therefore, it is possible to state that, in the first year of treatment, ATX causes a significantly greater growth delay than MPH. Additionally, both drugs showed a cumulative effect over time. After 24 months, the z -score had halved for both groups. Our results are in accordance with other studies Spencer et al. Although this finding is also confirmed by a recent review Faraone , a recent naturalistic study did not support any association between deficits in growth process and psychostimulant treatment in ADHD patients Villarreal et al. As for ATX, a meta-analysis of long-term studies of ATX in children showed that the stronger negative effect occurred after 18 months of treatment, and that then this effect decreased with time Spencer et al. A recent randomized, double-blind, placebo-controlled study of a Japanese pediatric population showed that the mean height increases in the ATX group were lower than those in the placebo group Takahashi et al. On the other hand, one placebo-controlled trial did not show clinically significant effects on growth rate with ATX Donnelly et al. Our results should be considered in the light of study limitations. First, it is not clear whether the observed slowdown in growth is a transient effect or a permanent potential reduction for individual growth with respect to the final height. As our observation time was only 24 months of follow-up, we were not able to evaluate if the negative effect on growth persisted after 24 months of treatment. Second, we could not assess if the negative effect observed on height would persist after permanent discontinuation of drugs Safer et al. Unfortunately, our study did not include a specific follow-up for subjects with permanent discontinuation of treatment. Statistically significant differences were observed only for depression in the weight analysis and for anxiety in the height analysis. Therefore, we believe that the population included in the analysis was representative of the whole population enrolled in the Italian ADHD National Registry. Both drugs cause a moderate slowdown in the height velocity highlighted by the values of the z -score. On the other hand, both drugs cause an increase in the average weight in pharmacologically treated patients. This finding should be confirmed by a randomized controlled study with two active drug arms and one control group. Regular monitoring of growth parameters parent's height, height, and weight measurements is recommended for all patients, but it should be strongly recommended for subjects treated with ADHD drugs. So far, attention has been focused on the effect of ADHD medications on height growth. In view of our findings, it is necessary to devote the same attention to the risk of onset of obesity in patients treated with these drugs. We thank all participating regional reference centers: Region Liguria Dr. Barbara Bobba, Dr. Edvige Veneselli, Dr. Maria Giulia Torrioli, Dr. Stefano Vicari, Dr. Sandro Bartolomeo, Prof. Paolo Curatolo, Prof. Anna Fabrizi, Dr. Dora Suglia, Dr. Modena Nicoletta, Dr. Paolo Stagi, Dr. Flaviana Murru, Dr. Andrea Tullini, Dr. Simona Chiodo, Dr. Antonio Pirisi , region Veneto Dr. Bernardo Dalla Bernardina, Dr. Dino Maschietto, Dr. Antonio Condini, Dr. Maurizio Brighenti, Dr. Piergiorgio Miottello, Dr. Andrea Gemma , region Sicilia Dr. Sebastiano Musumeci, Dr. Francesca Vanadia, Dr. Giancarlo Costanza, Dr. Donatella Ragusa, Dott. Filippo Calamoneri, Prof. Ferruccio Giaccherini, Dr. Marco Carrozzi, Dr. Silvana Cremaschi , region Lombardia Dr. Alberto Ottolini, Dr. Daniele Arisi, Dr. Alessandra Tiberti, Dr. Maria L. Terragni, Dr. Paola Morosini, Dr. Corrado Meraviglia, Prof. Carlo Lenti, Dr. Marco Pezzani, Prof. Umberto Balottin, Prof. Paolo Piccinelli, Dr. Giuseppe Chiarenza, Dr. Emilio Brunati, Dr. Vincenzo Montrasio, Dr. Massimo Molteni, Dr. Francesco Rinaldi, Dr. Giorgio Rossi, Dr. Roberto Segala , region Piemonte Dr. Flavio Guccione, Dr. Paolo Bailo, Dr. Dante Besana, Dr. Bianca Bassi, Dr. Marco Rolando, Dr. Laura Jarre, Dr. Francesca Ragazzo , region Sardegna Prof. Alessandro Zuddas, Prof. Massimo Tondi , province Alto Adige Dr. Gianluca Casara, Dr. Giovanni Voltolin , region Abruzzo Dr. Maria Pia Legge, Prof. Enzo Sechi, Dr. Elena Gennaro , region Calabria Dr. Giovanna Campolo, Dr. Antonio La Vitola, Dr. Annalisa Mingolla , region Puglia Dr. Angelo Spina, Prof. Lucia Margari, Dr. Angelo Massagli , region Campania Dr. Carmela Bravaccio, Dr. Rosario Granato, Dott. Giovanni Mazzotta , region Toscana Dr. Gabriele Masi, Prof. Giovanni Cioni , and region Marche Dr. Maurizio Pincherle, Dr. Cardinali Cesare, Dr. Vera Stoppioni, Dr. Tasca Rosolino. We also thank Mrs. Federica Maria Regini for editorial assistance and Dr. As a library, NLM provides access to scientific literature. J Child Adolesc Psychopharmacol. Find articles by Elena AP Germinario. Find articles by Romano Arcieri. Find articles by Maurizio Bonati. Find articles by Alessandro Zuddas. Find articles by Gabriele Masi. Find articles by Stefano Vella. Find articles by Flavia Chiarotti. Find articles by Pietro Panei. Copyright , Mary Ann Liebert, Inc. Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel.

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Cagliari buying MDMA pills

The proliferation of novel psychoactive substances NPS in the drug market raises concerns about uncertainty on their pharmacological profile and the health hazard linked to their use. Within the category of synthetic stimulant NPS, the phenethylamine 2-Cl-4,5-methylenedioxymethamphetamine 2-Cl-4,5-MDMA has been linked to severe intoxication requiring hospitalization. Thereby, the characterization of its pharmacological profile is urgently warranted. By in vivo brain microdialysis in adolescent and adult male rats we investigated the effects of 2-Cl-4,5-MDMA on dopamine DA and serotonin 5-HT neurotransmission in two brain areas critical for the motivational and rewarding properties of drugs, the nucleus accumbens NAc shell and the medial prefrontal cortex mPFC. Moreover, we evaluated the locomotor and stereotyped activity induced by 2-Cl-4,5-MDMA and the emission of kHz ultrasonic vocalizations USVs to characterize its affective properties. Furthermore, 2-Cl-4,5-MDMA stimulated locomotion and stereotyped activity in both adolescent and adult rats, although to a greater extent in adolescents. This is the first pharmacological characterization of 2-Cl-4,5-MDMA demonstrating that its neurochemical and behavioral effects may differ between adolescence and adulthood. These preclinical data could help understanding the central effects of 2-Cl-4,5-MDMA by increasing awareness on possible health damage in users. The opposite was observed on dialysate 5-HT in the NAc shell, with adolescents being more responsive than adults. Data will be helpful to understand and prevent health damage in 2-Cl-4,5-MDMA users of different ages. NPS can be either analogous to existing controlled drugs or new chemicals synthesized to mimic the effects of controlled drugs, thus evading drug control policies. The proliferation of NPS in the global market poses a serious health hazard and raises concerns over uncertainty about their toxicity and clinical treatment of NPS-induced intoxication Al-Banaa et al. NPS have been divided into four main classes based on their psychopharmacological effects: cannabinoids, depressants, hallucinogens, and stimulants Tracy et al. Alternatively, NPS can be categorized into six groups based on their chemical structure: alkylindoles, arylcyclohexylamines, phenethylamines, piperazines, synthetic cathinones, and tryptamines Miliano et al. Phenethylamines may act as either stimulants or hallucinogens but also possess entactogenic effects Schifano et al. Afterward, a case report of a year-old male polydrug user transported to hospital in a state of unconsciousness and hypoxia and displaying bradycardia and hypoventilation raised concerns, since toxicological analysis detected 2-Cl-4,5-MDMA in his urine Maresova et al. Considering the bulk of preclinical studies that demonstrate the existence of severe neurotoxic effects of MDMA Lyles and Cadet, ; Costa and Golembioskwa, and brain dysfunctions, serotonin syndrome, and hepatotoxicity linked to the use and misuse of MDMA Liechti, ; Patel et al. MDMA and analogs are usually consumed for their ability to increase empathy, sociability, and perceptions of sounds and colors and to induce mild hallucinations Green et al. Adolescence is a critical period of brain development, highly sensitive to the rewarding effects of drugs Corongiu et al. We followed this approach because DA transmission in the NAc shell and mPFC crucially mediates the rewarding and addictive properties of drugs of abuse Di Chiara et al. This study also aimed to identify possible differences between the responsiveness of adolescent and adult subjects to the neurochemical and behavioral effects of 2-Cl-4,5-MDMA. A total of 37 adolescent 5—7 weeks and 40 adult 10—12 weeks male Sprague-Dawley rats Envigo, San Pietro al Natisone, Italy were used for in vivo microdialysis or behavioral tests. Tap water and standard laboratory chow were provided ad libitum. All efforts were made to minimize pain and suffering and to reduce to the lesser extent the number of animals used. Quantification was made by comparison of a standard curve performed for each neurotransmitter. After placement in the cages, rats were allowed to habituate for 30 minutes and then administered with vehicle i. Locomotor activity was scored by counting the single or total number of beam interruptions. A further behavioral analysis i. Scoring was performed by recording the percentage of time spent in each behavioral category considered in 10 minutes intervals for the total time of observation 60 minutes. Behavioral items observed were: locomotion, rearing, sniffing up, repetitive and confined sniffing down, gnawing, flat body posture, Straub tail, and hind limb abduction. Intensity gain was always kept at a constant level throughout recordings. Data were tested for normal distribution using Shapiro—Wilk test. The effect of treatment e. To evaluate the effect of age on DA or 5-HT response within each brain area and 2-Cl-4,5-MDMA dose, an overall analysis of DA and 5-HT levels data obtained from each rat during the microdialysis experiment was conducted by calculating the area under the curve AUC , obtained by plotting the values of DA or 5-HT levels vs time with the classical trapezoidal rule and then comparing the obtained values by Holm-Sidak corrected multiple paired t tests. Behavioral scores were analyzed by factorial ANOVA for each behavioral item, with treatment and age as independent factors. Possible preexisting group differences in locomotor activity and USV emissions were analyzed by using unpaired Student's t -test. At first, we studied the effects of 3 i. In parallel, we studied the effect of an i. No significant differences between vehicle and 2-Cl-4,5-MDMA groups were observed in locomotor activity during the 30 minutes time of habituation to the motility cages Figure 5c , d. Upper panels a, b show the time-course of locomotor activity counts following vehicle and 2-Cl-4,5-MDMA administration. Inset panels c, d show activity counts during the 30 minutes of habituation to the motility cages. Lower panels e, f show the percentage of time spent in each behavioral item during the total time of observation 60 minutes. Similarly, no significant differences in calling behavior of the kHz USVs type were observed between vehicle and 2-Cl-4,5-MDMA groups during habituation to the motility cages Figure 6d , e. Abbreviation: USVs, ultrasonic vocalizations. In particular, 2-Cl-4,5-MDMA more markedly increased the extracellular levels of DA in both the NAc shell and mPFC of adult than adolescent rats, while the opposite was observed on extracellular levels of 5-HT in the NAc shell, with a more marked increase in adolescent than adult rats. In addition, 2-Cl-4,5-MDMA stimulated locomotor and stereotyped activity in both adolescent and adult rats, although adolescent rats spent higher percentages of time performing locomotion, sniffing up, and Straub tail than adult rats. The main results of this study were obtained by in vivo brain microdialysis that allowed to simultaneously evaluate in the same animal the changes of DA and 5-HT transmission in two brain areas that critically interact to encode motivated behaviors and responsiveness to motivational stimuli De Luca, and whose interplay may differ between adolescence and adulthood. The ability to increase DA in the NAc shell is a common feature of substances with abuse potential and is considered an index of the reinforcing and addictive properties of a drug Carlezon and Wise, ; Di Chiara et al. The quantification of 5-HT from the NAc shell showed a higher responsiveness of adolescent than adult rats, while no age-dependent differences were observed in the mPFC. Notably, the peculiar response of 5-HT transmission in the NAc shell of adolescent rats displayed a prolonged and a 4-fold higher increase in 5-HT release than adult rats, whereas no age-related differences in this response were observed in the mPFC. Reasons for the higher responsiveness of the 5-HT system in adolescent rats may be searched in the light of several factors. It should be considered that 5-HT is one of the first neurotransmitter systems to develop in the mammalian brain and that it plays an important role in brain development Lauder , ; Rubenstein, Animal studies have shown that 5-HT content, SERT levels, and 5-HT binding sites are all generally higher in the developing brain compared with the adult brain and that before puberty they all decline to levels similar to those found in the adult brain Murrin et al. Nonetheless, although the 5-HT system appears to be mature early in life as regard fiber density and 5-HT synthesis, each of 5-HT receptors and enzymes have a unique pattern of development, with some stabilizing before puberty Galineau et al. Serotonergic innervation of the rat cerebral cortex begins to show patterns characteristic of the adult cortex by the end of the third postnatal week Dori et al. While the latter finding is consistent with our results showing no differences in 5-HT release in the mPFC following 2-Cl-4,5-MDMA, the early development of 5-HT neuronal system does not explain the striking differences in 5-HT responsiveness in the NAc shell between adolescent and adult rats. While not neglecting the several changes occurring in the adolescent brain in neuronal systems other than the 5-HT system, which might interact with and affect 5-HT neurotransmission, one likely explanation for the greater increase of 5-HT observed in the NAc shell of adolescent rats might be linked to the contribution of oxytocin OT. The OT system is implicated in social behavior Sanna and De Luca, and, as other neuronal systems, it undergoes changes during brain development with a significant phase of transition following puberty Sannino et al. Other in vivo studies showed that systemic Parsons et al. Of note, repeated treatment with cocaine sensitizes both 5-HT and DA increase in the NAc and dorsal raphe nucleus in response to cocaine challenge Parsons and Justice, a , b ; De Luca et al. Taken together, the above evidence could suggest that an interplay exists between the marked increase of 5-HT outflow and the low increase of DA outflow in the NAc shell of adolescent rats observed here after the administration of 2-Cl-4,5-MDMA. Indeed, adolescence is the phase of neurodevelopment when the PFC matures, being PFC a key regulator of superior brain functions that are altered in psychiatric disorders Renard et al. Furthermore, since in vivo studies have demonstrated the neurotoxicity of molecules structurally-correlated to 2-Cl-4,5-MDMA Cadoni et al. Our results on the behavioral effects of 2-Cl-4,5-MDMA have shown that it stimulates locomotor activity and induces the appearance of stereotypies in both adolescent and adult rats. Regarding locomotor activity, it is well known that activation of DA transmission in the NAc stimulates locomotion through an action on D1 and D2 receptors Sharp et al. Similarly, increased 5-HT transmission by indirect 5-HT agonists is able to stimulate locomotor activity through a 5-HT1B mediated mechanism Geyer, Moreover, adolescent rats displayed a significantly greater increase in the time spent performing locomotion, rearing, and sniffing up compared with adult rats. Regarding stereotypes linked to 5-HT release Straub tail, hind limb abduction, and flat body posture , we observed a comparable hind limb abduction in adolescent and adult rats and a more marked Straub tail in adolescents compared with adults. This effect is similar to what was observed in previous studies after both acute and repeated administration of MDMA Sadananda et al. At the same time, only drugs that markedly activate DA transmission in the NAc shell i. The emission of kHz USVs is considered a behavioral marker of the positive effects that psychoactive drugs may elicit on arousal, affect, and motivation in rats Simola, Nevertheless, it is noteworthy that several drugs that increase the affective and motivational state of rats scarcely stimulate the emission of kHz USVs Wright et al. Accordingly, the lack of effect of 2-Cl-4,5-MDMA on calling behavior should not be simply considered a result indicating that this NPS has no influence on the affective state of rats. Conversely, it may rather support the assumption suggested by microdialysis data that 2-Cl-4,5-MDMA has a psychopharmacological profile different from that of other psychostimulants of abuse. This study has some limitations since it focused mainly on neurochemical and behavioral effects induced by the acute administration of 2-Cl-4,5-MDMA, without addressing the underlying molecular mechanisms, as well as the possible involvement of active metabolites in the findings observed. Moreover, we used only male rats in our study and, therefore, we do not know if our findings can be extended to female rats. Nevertheless, this study completes previous investigations on the pharmacological and toxicological properties of 2-Cl-4,5-MDMA Sogos et al. This feature may influence the pattern of use and misuse of 2-Cl-4,5-MDMA, such as the frequency of ingestion, but also the psychoactive acute effects of this NPS that appear dissimilar from those of other psychostimulant drugs Miliano et al. The data underlying this article will be shared on reasonable request by the corresponding author. A time series analysis. Int J Drug Policy 77 : Google Scholar. 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Neuropharmacology 63 : — Simola N , Frau L , Plumitallo A , Morelli M Direct and long-lasting effects elicited by repeated drug administration on kHz ultrasonic vocalizations are regulated differently: implications for the study of the affective properties of drugs of abuse. Int J Neuropsychopharmacol 17 : — Int J Mol Sci 22 : Curr Opin Behav Sci 13 : — J Child Neurol 15 : — Behav Brain Res : 64 — Pharmacol Ther : BMJ : i United Nations Publication , 87 — Google Preview. Neuropharmacology 65 : 58 — Epub Sep 7. Erratum in: Neuropharmacology. Van Bockstaele EJ , Pickel VM Ultrastructure of serotonin-immunoreactive terminals in the core and shell of the rat nucleus accumbens: cellular substrates for interactions with catecholamine afferents. J Comp Neurol : — Wahlstrom D , Collins P , White T , Luciana M Developmental changes in dopamine neurotransmission in adolescence: behavioral implications and issues in assessment. Brain Cogn 72 : — Prog Brain Res : — Williams SN , Undieh AS Brain-derived neurotrophic factor signaling modulates cocaine induction of reward-associated ultrasonic vocalization in rats. J Psychopharmacol 20 : — Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign in through your institution. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Interest Statement. Data Availability. Author Contributions. Journal Article. Gessica Piras , Gessica Piras. Department of Biomedical Sciences, University of Cagliari. Oxford Academic. Cristina Cadoni. Francesca Caria. Nicholas Pintori. Enrica Spano. Maksims Vanejevs. Latvian Institute of Organic Synthesis. Anastasija Ture. Graziella Tocco. Nicola Simola. Maria Antonietta De Luca. Editorial decision:. Corrected and typeset:. Select Format Select format. Permissions Icon Permissions. Abstract Background. Graphical Abstract. Open in new tab Download slide. Addiction , dopamine , novel psychoactive substances , serotonin , ultrasonic vocalizations. Significance Statement. Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Effect of the UK Psychoactive Substances Act on episodes of toxicity related to new psychoactive substances as reported to the National Poisons Information Service. Google Scholar Crossref. Search ADS. Topographical dopamine and serotonin distribution and turnover in rat striatum. Serotonin-facilitated dopamine release in vivo: Pharmacological characterization. Google Scholar PubMed. Genetic and early environmental influences on the serotonin system: consequences for brain development and risk for psychopathology. Ultrastructural localization of tyrosine hydroxylase in rat nucleus accumbens. Behavioural sensitization after repeated exposure to Delta 9-tetrahydrocannabinol and cross-sensitization with morphine. Widespread reduction of dopamine cell bodies and terminals in adult rats exposed to a low dose regimen of MDMA during adolescence. Mapping of locomotor behavioral arousal induced by microinjections of dopamine within nucleus accumbens septi of rat forebrain. Rewarding actions of phencyclidine and related drugs in nucleus accumbens shell and frontal cortex. Adolescence versus adulthood: differences in basal mesolimbic and nigrostriatal dopamine transmission and response to drugs of abuse. Neuronal and peripheral damages induced by synthetic psychoactive substances: an update of recent findings from human and animal studies. The novel psychoactive substance methoxetamine induces persistent behavioral abnormalities and neurotoxicity in rats. Serotonin enhances striatal dopamine outflow in vivo through dopamine uptake sites. De Luca. Influence of morphine sensitization on the responsiveness of mesolimbic and mesocortical dopamine transmission to appetitive and aversive gustatory stimuli. Di Chiara. Abuse of licit and illicit psychoactive substances in the workplace: medical, toxicological, and forensic aspects. Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Regional differences in the ontogeny of the serotonergic projection to the cerebral cortex. Ontogeny of the dopamine and serotonin transporters in the rat brain: an autoradiographic study. Experimental strategies to discover and develop the next generation of psychedelics and entactogens as medicines. Neurotransmitter regulation of dopamine neurons in the ventral tegmental area. Mephedrone, compared with MDMA ecstasy and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats. Changes in the adolescent brain and the pathophysiology of psychotic disorders. Ontogeny of the serotonergic system in the rat: serotonin as a developmental signal. Neurotransmitters as growth regulatory signals: role of receptors and second messengers. Sex differences in abuse-related neurochemical and behavioral effects of 3,4-methylenedioxymethamphetamine MDMA in rats. The identification of 2-chloro-4,5-methylenedioxymethylamphetamine in an illicit drug seizure. Neuropharmacology of New Psychoactive Substances NPS : focus on the rewarding and reinforcing properties of cannabimimetics and amphetamine-like stimulants. Comparison of the maturation of the adrenergic and serotonergic neurotransmitter systems in the brain: implications for differential drug effects on juveniles and adults. Oxytocin-dependent reopening of a social reward learning critical period with MDMA. Serotonin1B receptors in the ventral tegmental area modulate cocaine-induced increases in nucleus accumbens dopamine levels. Perfusate serotonin increases extracellular dopamine in the nucleus accumbens as measured by in vivo microdialysis. Serotonin and dopamine sensitization in the nucleus accumbens, ventral tegmental area, and dorsal raphe nucleus following repeated cocaine administration. The role of dopamine and endocannabinoid systems in prefrontal cortex development: Adolescence as a critical period. Light microscopic immunocytochemical evidence of converging serotonin and dopamine terminals in ventrolateral nucleus accumbens. The synthesis and characterisation of MDMA derived from a catalytic oxidation of material isolated from black pepper reveals potential route specific impurities. Long-term consequences of adolescent cannabinoid exposure in adult psychopathology. Age of initiation and substance use progression: A multivariate latent growth analysis. Lifespan oxytocin signaling: maturation, flexibility, and stability in newborn, adolescent, and aged brain. Serotonin-dopamine interactions in the control of conditioned reinforcement and motor behavior. MDMA self-administration in laboratory animals: a summary of the literature and proposal for future research. A direct comparison of amphetamine-induced behaviors and regional brain dopamine release in the rat using intracerebral dialysis. Rat ultrasonic vocalizations and behavioral neuropharmacology: from the screening of drugs to the study of disease. Rat kHz ultrasonic vocalizations as a tool in studying neurochemical mechanisms that regulate positive emotional states. Emission of categorized kHz ultrasonic vocalizations in rats repeatedly treated with amphetamine or apomorphine: possible relevance to drug-induced modifications in the emotional state. Pharmacological characterization of kHz ultrasonic vocalizations in rats: comparison of the effects of different psychoactive drugs and relevance in drug-induced reward. Direct and long-lasting effects elicited by repeated drug administration on kHz ultrasonic vocalizations are regulated differently: implications for the study of the affective properties of drugs of abuse. Human neuronal cell lines as an in vitro toxicological tool for the evaluation of novel psychoactive substances. Developmental changes in cerebrospinal fluid concentrations of monoamine-related substances revealed with a Coulochem electrode array system. Amphetamine-induced 50 kHz calls from rat nucleus accumbens: a quantitative mapping study and acoustic analysis. Adolescent neurodevelopment and substance use: Receptor expression and behavioral consequences. Van Bockstaele. Ultrastructure of serotonin-immunoreactive terminals in the core and shell of the rat nucleus accumbens: cellular substrates for interactions with catecholamine afferents. Developmental changes in dopamine neurotransmission in adolescence: behavioral implications and issues in assessment. Serotonin, norepinephrine and associated neuropeptides: effects on somatic motoneuron excitability. Brain-derived neurotrophic factor signaling modulates cocaine induction of reward-associated ultrasonic vocalization in rats. Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population. Failure of rewarding and locomotor stimulant doses of morphine to promote adult rat kHz ultrasonic vocalizations. Endogenous serotonin stimulates striatal dopamine release in conscious rats. For commercial re-use, please contact reprints oup. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals. Issue Section:. Download all slides. Supplementary data. Views More metrics information. Total Views Email alerts Article activity alert. Advance article alerts. New issue alert. In progress issue alert. 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