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Behavioral studies have implicated central dopaminergic systems, especially the ventral tegmental area of Tsai VTA , in the mediation of the reinforcing effects of drugs of abuse such as cocaine. A brain slice preparation of the VTA was used to assess the direct effects of cocaine on the spontaneous activity of dopamine-type neurons. While there was a considerable variability in the response to a given concentration of cocaine among the individual units, every cell inhibited by dopamine was also inhibited by cocaine. The local anesthetic lidocaine had variable effects on firing rate, but never potentiated the inhibitory effects of dopamine. Inhibitory responses to either dopamine or cocaine were blocked by the specific D2 dopamine receptor antagonist sulpiride. Small concentrations of cocaine 0. Furthermore, the inhibitory action of apomorphine on spontaneous activity in the VTA was not potentiated by cocaine. These observations suggest that in low concentrations, cocaine can act as a dopamine reuptake inhibitor in the VTA, and that the resultant increase in extracellular dopamine acts upon dopamine autoreceptors to inhibit cellular activity. This is a preview of subscription content, log in via an institution to check access. Rent this article via DeepDyve. Institutional subscriptions. Albanese A, Minciacchi D Organization of the ascending projections from the ventral tegmental area: a multiple fluorescent retrograde tracer study in the rat. J Comp Neurol — Brain Res — Soc Neurosci Abstr Google Scholar. Brodie MS, Dunwiddie TV The effects of cocaine on ventral tegmental area spontaneous activity in vitro: Interactions with dopamine, sulpiride and cholecystokinin. Brodie MS, Dunwiddie TV Cholecystokinin potentiates dopamine inhibition of mesencephalic dopamine neurons in vitro. Carter DA, Fibiger HC Ascending projections of presumed dopamine-containing neurons in the ventral tegmentum of the rat as demonstrated by horseradish peroxidase. Neuroscience — Dahlstrom A, Fuxe K Evidence for the existence of monoamine-containing neurons in the central nervous system. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand 62 Suppl :1— J Neurophysiol — Einhorn LC, White FJ Electrophysiological effects of cocaine in the mesoaccumbens dopamine system: Studies in the ventral tegmental area. Einhom LC, White FJ Electrophysiological effects of cocaine in the mesoaccumbens dopamine system: Studies in the ventral tegmental area. J Neurosci — Science — Action potential generating mechanisms and morphological correlates. CAS Google Scholar. Biochem Pharmacol — Iversen LL Uptake mechanisms for neurotransmitter amines. J Physiol Lond — Br J Pharmacol — Llinas R, Greenfield SA, Jahnsen H Electrophysiology of pars compacta cells in the in vitro substantia nigra — a possible mechanism for dendritic release. Maeda H, Mogenson GJ An electrophysiological study of inputs to neurons of the ventral tegmental area from the nucleus accumbens and medial preoptic-anterior hypothalamic areas. Matthews RT, German DC Electrophysiological evidence for excitation of rat ventral tegmental area dopamine neurons by morphine. Psychopharmacology — Phillipson OT Afferent projections to the ventral tegmental area of Tsai and interfascicular nucleus: a horseradish peroxidase study in the rat. Pinnock RD Hyperpolarizing action of baclofen on neurons in the rat substantia nigra slice. Pitts DK, Marwah J a Effects of cocaine on single spontaneously firing central monoaminergic neurons. Pitts DK, Marwah J b Effects of cocaine on the electrical activity of single noradrenergic neurons from locus coeruleus. Life Sci — Pharmacol Biochem Behav — Roberts DCS, Koob GF Disruption of cocaine self-administration following 6-hydroxydopamine lesions of the ventral tegmental area in rats. Eur J Pharmacol — J Pharmacol Exp Ther — Strichartz G Molecular mechanisms of nerve block by local anesthetics. Anesthesiology — Suppes T, Pinnock RD Sensitivity of neuronal dopamine response in the substantia nigra and ventral tegmentum to clozapine, metoclopramide and SCH Neuropharmacology — Wang RY a Dopaminergic neurons in the rat ventral tegmental area. Identification and characterization. Brain Res Rev — Wang RY b Dopaminergic neurons in the rat ventral tegmental area. Evidence for autoregulation. Wang RY c Dopaminergic neurons in the rat ventral tegmental area. Effects of D- and l. White FJ Electrophysiological effects of cocaine in the mesoaccumbens dopamine system: Studies in the nucleus accumbens. White FJ, Wang RY A10 dopamine neurons: role of autoreceptors in determining firing rate and sensitivity to dopamine agonists. Wise RA Catecholamine theories of reward: A critical review. Neurosci Lett — Download references. You can also search for this author in PubMed Google Scholar. Reprints and permissions. Brodie, M. Cocaine effects in the ventral tegmental area: Evidence for an indirect dopaminergic mechanism of action. Naunyn-Schmiedeberg's Arch Pharmacol , — Download citation. Received : 20 April Accepted : 31 July Issue Date : December Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Home Naunyn-Schmiedeberg's Archives of Pharmacology Article Cocaine effects in the ventral tegmental area: Evidence for an indirect dopaminergic mechanism of action Published: December Volume , pages —, Cite this article. Summary Behavioral studies have implicated central dopaminergic systems, especially the ventral tegmental area of Tsai VTA , in the mediation of the reinforcing effects of drugs of abuse such as cocaine. Access this article Log in via an institution. Circuit specificity in the inhibitory architecture of the VTA regulates cocaine-induced behavior Article 23 January Effects of abstinence from chronic cocaine self-administration on nonhuman primate dorsal and ventral noradrenergic bundle terminal field structures Article 27 May References Albanese A, Minciacchi D Organization of the ascending projections from the ventral tegmental area: a multiple fluorescent retrograde tracer study in the rat. Author information Author notes Mark S. Dunwiddie Authors Mark S. Brodie View author publications. View author publications. Additional information Send offprint requests to T. Rights and permissions Reprints and permissions. About this article Cite this article Brodie, M. Copy to clipboard. 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drugs of abuse such as cocaine. A brain slice preparation of the VTA was used to assess the direct effects of cocaine on the spontaneous activity of.
Brain tissue and blood collected from trunk vessels were used to measure cocaine and BZE levels (see Supplementary materials for details). Drugs.
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