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The vaccine is designed to help produce anti-cocaine antibodies in the body of a person who is chemically dependent on the substance. Scientists in Brazil have announced the development of an innovative new vaccine to treat addiction to cocaine and its powerful derivative, crack. Dubbed 'Calixcoca,' the treatment, which has shown promising results in trials on animals, triggers an immune response that blocks cocaine and crack from reaching the brain. In simple terms, the vaccine would work by preventing addicts from getting high from the drug. According to Frederico Garcia, a psychiatrist and coordinator of the project at the Federal University of Minas Gerais in Brazil, if the treatment gets regulatory approval, it would mark the first time cocaine addiction is treated using a vaccine. The vaccine works by triggering patients' immune systems to produce antibodies that bind to cocaine molecules in the bloodstream, making them too large to pass into the brain's mesolimbic system, or 'reward centre,' where the drug normally stimulates high levels of pleasure-inducing dopamine. Similar studies have been carried out in the United States which is the world's top cocaine consumer according to the United Nations Office on Drugs and Crime. But these efforts stalled when clinical trials did not demonstrate sufficient results, among other reasons, Garcia said. Calixcoca has so far proven effective in testing on animals, producing significant levels of antibodies against cocaine and few side effects. Researchers also found that it protected rat fetuses against cocaine suggesting that it could be used in humans to protect the unborn babies of pregnant addicts. We currently use a combination of psychological counseling, social assistance and rehabilitation, when necessary,' he said. Garcia believes Calixcoca could add an important tool to that regimen by helping patients at critical stages of recovery, such as when they leave rehab. The vaccine is made with chemical compounds designed in the lab, rather than biological ingredients, meaning it would be less expensive to produce than many vaccines and would not have to be stored at cold temperatures. The exact target group will depend on the outcome of clinical trials, but is theoretically meant to be recovering addicts 'who are off cocaine and want to stay that way,' he said. Given the stakes, anticipation around the vaccine is high. More than 3, people have contacted Garcia's team to volunteer to take part in the clinical trials. By Euronews and AFP. Share this article Comments. Share this article. You might also like Now playing Next. Health news. Now playing Next. World News. Medical research Brazil cocaine Drugs Vaccine addiction.

Scientists in Brazil are developing the first vaccine that could help break cocaine addiction

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Prenatal exposure to cocaine has been reported to produce long-lasting cognitive deficits, but the underlying mechanisms remain largely unknown. Prenatal cocaine exposure also leads to enhanced mPFC pyramidal neuronal excitability. However, the development of behavioural sensitization to repeated cocaine administration was impaired in rats that were exposed to cocaine in utero. These results suggest that prenatal cocaine exposure causes a long-lasting reduction of GABAergic inhibition in mPFC layer V pyramidal neurons, leading to an increased susceptibility of excitatory synapses to LTP induction during the postnatal period. Illicit drug use by pregnant women continues to be a major epidemiological concern in the developed countries. Although the extent to which prenatal cocaine exposure affects fetal development remains a matter of significant controversy, numerous studies have reported that cocaine exposure in utero can result in a wide range of cognitive deficits such as memory impairments, impulsivity, and difficulties in modulating attention, in both human Leech et al. However, the consequence and underlying neurobiological mechanisms by which prenatal cocaine exposure causes cognitive deficits remain largely unknown. The prefrontal cortex PFC is thought to subserve a wide range of cognitive processes, including working memory Goldman-Rakic, , selection and remembering of relevant stimuli Rainer et al. In addition, recent studies have implicated an important role of the mPFC in the development of cocaine-induced locomotor sensitization and addiction Huang et al. Furthermore, it was hypothesized that the mPFC is one potential candidate site for the adverse effects of prenatal cocaine exposure on cognitive functions. Several lines of previous observations support this hypothesis. First, Roth and colleagues showed that prenatal exposure to cocaine is associated with a dramatic increase in the number of activated mPFC neurons of rats, as indicated by expression of the immediate early gene, c -fos , in response to environmental stimuli Morrow et al. However, it is currently unclear whether prenatal cocaine exposure affects neuronal excitability and the induction of long-term synaptic plasticity at mPFC excitatory synapses. Considering that alterations of long-term synaptic plasticity may contribute the deficits in cognitive functions, we were interested in determining the effect of prenatal cocaine exposure on the induction of mPFC long-term potentiation LTP. Prenatal cocaine treatments were as previously described Morrow et al. Briefly, timed-pregnant Sprague—Dawley rats were given intravenous injections of either saline 0. Offspring from each treated dam were fostered to a non-treated foster dam at birth and then weaned at around postnatal day PD The number of pups was culled to eight per group four males, four females. No significant physical differences were noted between the prenatal saline- and cocaine-treated rat pups. Most experiments unless indicated otherwise were performed on PD Only male rats were used in each experiment. For electrophysiological recordings, slices were transferred to a submerged recording chamber and fixed at the glass bottom of the chamber with a nylon grid on a platinum wire frame. The chamber consisted of a circular well of low volume 1—2 ml and was perfused constantly at Whole-cell recordings were made from layer V pyramidal neurons of the mPFC by using a patch-clamp amplifier Axopatch B, Axon Instruments, USA under infrared differential interference contrast optics. Electrical signals were low-pass filtered at 2 kHz, digitized at 10 kHz using a bit analog-to-digital converter Digidata , Axon Instruments. Patch pipettes were pulled from borosilicate capillary tubing and heat polished. The experimenter was blinded to the prenatal treatment throughout the recordings and analyses. The spike-timing protocol for LTP induction consisted of 10 bursts of EPSP-spike pairs, with each burst consisting of five paired stimuli delivered at ms intervals 20 Hz and an inter-burst interval of 10 s as described previously Huang et al. The post-synaptic spikes were evoked by injection of depolarizing current pulses 1—2 nA, 2—4 ms , with the onset of EPSPs preceding the peak of post-synaptic spikes by 10 ms. Evoked EPSPs were sampled at 0. Locomotor activity was measured as described previously Huang et al. Elevated plus maze experiments were performed as described previously Pellow et al. See Supplementary material for further information. Western blotting analysis was performed as described previously Huang et al. The dose was selected on the basis of published studies Morrow et al. The number of animals used is indicated by n. Statistical comparisons of the synaptic currents were made using the Kolmogorov—Smirnov KS test. In the first series of experiments, we examined whether prenatal cocaine exposure alters the induction of LTP at mPFC excitatory synapses during the postnatal period. This pattern of stimulation was used to mimic bursting activity observed in PFC neurons in vivo Fuster, ; Kitano et al. We found that this paired stimulation protocol induced a strong and long-lasting increase of the slope of EPSPs in mPFC layer V pyramidal neurons in slices obtained from PD rats that were exposed to cocaine in utero Moreover, the facilitatory effect of prenatal cocaine exposure on LTP induction was noted at PD 16—18, reached maximal levels at PD 22—24, and remained evident at later ages Fig. The average magnitude of potentiation was 8. However, comparison of the synaptic strength following EPSP-spike pairing stimulation in slices from prenatal saline-treated rats at different postnatal ages revealed no significance differences. These results suggest that prenatal cocaine exposure can enhance LTP induction in mPFC pyramidal neurons and such facilitatory effect occurs progressively during the postnatal period. Since the facilitation of LTP by prenatal cocaine exposure occurred consistently during the age of PD , we therefore chose this age group to identify the underlying mechanisms of this event in all subsequent experiments. The right-hand panel shows a typical post-synaptic response during one burst of paired stimulation. Arrows indicate application of the LTP induction protocol. Representative traces of EPSPs were taken at the time indicated. Input resistance R i was monitored throughout the experiment middle panels. The magnitude of LTP was measured 30 min after induction. The total number of animals examined is indicated in parentheses. The dotted lines show the level of baseline. Error bars indicate standard error of the mean. Notably, the presence of BMI did not further increase the extent of LTP in slices from rats with prenatal cocaine exposure. Furthermore, application of zolpidem, a benzodiazepine agonist known to enhance the activation of GABA A receptors Depoortere et al. No LTP was induced in slices from rats prenatally treated with saline in the presence of zolpidem Data are presented in the same manner as in Fig. The lack of additive effects of BMI and prenatal cocaine exposure on the extent of potentiation induced by the spike-EPSP pairs is consistent with the idea that some of the mechanisms responsible for the enhanced LTP induction in the mPFC are shared. To investigate whether the increased susceptibility to LTP induction found in prenatal cocaine-treated rats is caused by the reduced GABA A receptor-mediated inhibition, we compared IPSCs recorded in mPFC pyramidal neurons in slices from prenatal saline- and cocaine-treated rats. Figure 3 a depicts the relationship between stimulus intensity and IPSC amplitude. Prenatal cocaine-treated rats showed a significant decrease in amplitude of IPSCs, compared to the corresponding age-matched prenatal saline-treated rats. Moreover, the cocaine-induced reduction in IPSC amplitude is probably of post-synaptic origin, because prenatal cocaine-treated rats showed a significant reduction of the amplitude of mIPSCs The mean frequency of mIPSCs was not significantly different between prenatal saline-treated 2. The amplitude of IPSCs was significantly reduced in prenatal cocaine-treated rats when compared to prenatal saline-treated rats. Each point is the average of six experiments. To determine whether prenatal cocaine exposure also caused a long-lasting reduction of GABA A receptor-mediated tonic inhibition, we compared GABA A receptor-mediated tonic currents recorded in mPFC pyramidal neurons in slices from prenatal saline- and cocaine-treated rats. The average amplitude of tonic currents were also decreased in mPFC pyramidal neurons in slices from prenatal cocaine-treated rats A straightforward hypothesis is that prenatal cocaine exposure leads to a persistent reduction of surface expression of GABA A receptors. As shown in Fig. We found no significant difference between prenatal saline- and cocaine-treated rats in either rise time or decay time constant of both evoked IPSCs saline: rise time 2. Consistent with the reduced GABAergic activity of mPFC pyramidal neurons, we found that the firing activity of these neurons by quantifying the number of action potentials in response to post-synaptic depolarizing current injection 1 nA, ms was significantly increased in slices from rats exposed to cocaine in utero However, no significant changes on membrane potential, action potential threshold, or kinetics were observed in mPFC pyramidal neurons from prenatal cocaine-treated rats during the postnatal period, compared to those of prenatal saline-treated rats. Top: representative traces of action potential firing elicited by a constant depolarizing current injection 1 nA, ms in mPFC layer V pyramidal neurons from rats exposed to saline or cocaine in utero. Bottom: summary of the number of action potentials by constant depolarizing current injection in slices from rats prenatally treated with saline or cocaine. To determine the potential neuropsychological impact of prenatal cocaine exposure during the postnatal period, we chose to examine the ability to develop behavioural sensitization. Prenatal cocaine exposure impairs the development of behavioural sensitization to repeated cocaine administration. After 3 d of saline injections for habituation to the chamber, control, prenatal saline-treated or prenatal cocaine-treated rats received daily injections of saline or cocaine for 5 d. Average percent time spent in b the open arms and c average total distance travelled in the elevated plus maze between prenatal saline- and cocaine-treated rats was measured. There were no significant differences between prenatal saline Sal - and cocaine Coc -treated rats in percent time spent in the open arms or total distance travelled in the elevated plus maze. Because a change in basal anxiety state may also alter the locomotor response, we therefore tested whether a difference existed between prenatal cocaine- and saline-treated rats in the elevated plus maze test, a behavioural model of untrained anxiety-like response. These results suggest that prenatal cocaine exposure does not alter the basal anxiety state. In the present study, we provide evidence for an enhancement of LTP induction in mPFC layer V pyramidal neurons of rats that were exposed to cocaine in utero. Furthermore, we show that cocaine exposure in utero results in an impairment of the development of behavioural sensitization to repeated cocaine administration during the postnatal period. This observation is consistent with previous reports that highlighted a prominent role of GABAergic activity in regulating the induction of LTP at several central excitatory synapses, including in the hippocampus Meredith et al. A similar adaptation has been observed in our previous study Huang et al. This reduced synaptic inhibition may increase the excitability of mPFC pyramidal neurons, leading to disruption of cortical rhythms that depend on a balance between excitation and inhibition Shu et al. Interestingly, the observed neuronal adaptations to prenatal cocaine exposure became progressively more noticeable after PD 16 and remained constant until prepubertal ages. GABA A receptor-mediated tonic inhibition has been observed in a variety of neuronal cell types, including granule cells of the cerebellum Kaneda et al. Our study is the first to assess changes in GABA A receptor-mediated tonic inhibition in mPFC pyramidal neurons following prenatal cocaine exposure and demonstrates an enduring reduction of tonic inhibition Fig. Although the present study demonstrates that prenatal cocaine exposure elevated excitatory synaptic transmission in the mPFC, there is yet no evidence for such a change being involved in the enhancement of LTP induction Lu et al. Changes in the sensitivity of the mesolimbic and mesocortical reward system to cocaine have been reported in prenatal cocaine-treated rats. For example, prenatal cocaine exposure has been shown to reduce locomotor sensitivity to postnatal cocaine challenge Crozatier et al. One potential mechanism that may account for such long-lasting adaptation is a reduction of dopamine D 1 receptor function. This idea has been further confirmed by a recent study revealing that prenatal cocaine-treated rats were less sensitive to the locomotor stimulant effects of the dopamine agonist apomorphine than prenatal saline-treated rats Lu et al. Our results provide further evidence for alterations in the development of cocaine-induced behavioural sensitization in prenatal cocaine-treated rats Fig. This finding is consistent with a previous study showing that chronic cocaine-induced behavioural sensitization and stereotypic behaviours in adult mice were altered by prenatal cocaine exposure Crozatier et al. However, it is not clear how prenatal cocaine exposure exerted its long-lasting effects on the development of behavioural sensitization. How does enhanced LTP relate to decreased behavioural sensitization to cocaine? In our previous study Huang et al. However, in the present study, we found that prenatal cocaine exposure resulted in increased susceptibility of excitatory synapses to LTP induction during the postnatal period but decreased behavioural sensitization to cocaine. The reason for this apparent disconnection is not clear but could be attributed to the fact that prenatal cocaine exposure activates some molecular mechanisms required to develop behavioural sensitization, which in turn occludes subsequent development of behavioural sensitization to cocaine during the postnatal period. Under this scenario, the locomotor sensitivity to cocaine should be reduced after prenatal cocaine exposure. Indeed, the present study and Lu et al. We could not exclude the possibility that enhanced LTP induction in the mPFC may also play a role in other behavioural responses to cocaine. A recent study by Lu et al. Although their results appear to be consistent with our findings, there are some differences between these two studies. Second, whether GABA A receptor-mediated tonic inhibition is altered by prenatal cocaine exposure was not examined in Lu et al. Third, we provided further evidence that prenatal cocaine exposure not only decreased the sensitivity of the locomotor activity to postnatal acute cocaine challenge but also impaired the development of behavioural sensitization to repeated cocaine administration. We also observe that cocaine exposure in utero decreased locomotor sensitization to cocaine and impaired the development of cocaine-induced behavioural sensitization. These findings may provide a new mechanistic framework to help understand the adverse effects reported with prenatal cocaine exposure on brain development and cognitive functions. Molecular Pharmacology 59 , — Google Scholar. Medial frontal cortex mediates perceptual attentional set shifting in the rat. Journal of Neuroscience 20 , — Dopamine gates LTP induction in lateral amygdala by suppressing feedforward inhibition. 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Journal of Neuroscience 17 , — Prenatal exposure to cocaine disrupts D 1A dopamine receptor function via selective inhibition of protein phosphatase 1 pathway in rabbit frontal cortex. Journal of Neuroscience 21 , — 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. Materials and methods. Statement of Interest. Journal Article. Prenatal cocaine exposure enhances long-term potentiation induction in rat medial prefrontal cortex. Oxford Academic. Ying-Ching Liang. Kuei-Sen Hsu. Address for correspondence: K. Hsu, Ph. Revision received:. Select Format Select format. Permissions Icon Permissions. Abstract Prenatal exposure to cocaine has been reported to produce long-lasting cognitive deficits, but the underlying mechanisms remain largely unknown. Open in new tab Download slide. Google Scholar PubMed. Google Scholar Crossref. Search ADS. Issue Section:. Download all slides. Views More metrics information. Total Views Email alerts Article activity alert. Advance article alerts. New issue alert. In progress issue alert. Receive exclusive offers and updates from Oxford Academic. Citing articles via Web of Science Working memory performance predicts, but does not reduce, cocaine- and cannabinoid-seeking in adult male rats. More from Oxford Academic. Science and Mathematics. Authoring Open access Purchasing Institutional account management Rights and permissions. Get help with access Accessibility Contact us Advertising Media enquiries.

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