Actions of cocaine on rat nucleus accumbens neurones in vitro.
1. Intracellular recordings were made from 103 neurones of the rat nucleus accumbens in vitro. 2. Dopamine (3-100 microM; in sulpiride, 1 microM) hyperpolarized neurones (79%) by acting at D1 receptors: dopamine (3-100 microM; in SCH23390, 1 microM) depolarized neurones (55%) by acting at D2 receptors. 5-Hydroxytryptamine (1-100 microM) depolarized 86% neurones. 3. Both actions of dopamine as well as the effect of 5-hydroxytryptamine were potentiated by cocaine (0.3-30 microM), which had no effect of its own on membrane potential. 4. Dose-ratio was computed as [(concentration of agonist causing a 4 mV potential change in cocaine)/(concentration of agonist causing a 4 mV potential change without cocaine)]. Cocaine (1-30 microM) caused the same dose-ratio whether dopamine depolarizations (D2) or hyperpolarizations (D1) were measured; the dose-ratio ranged from 2 (1 microM) to 50 (30 microM). 5. Responses to 5-hydroxytryptamine were increased more than responses to dopamine; cocaine 1 microM gave a dose-ratio of 13.4 and at 30 microM gave a dose-ratio of 118. 6. It is concluded that cocaine acts to inhibit the uptake of dopamine and 5-hydroxytryptamine in slices of rat nucleus accumbens; lower concentrations of cocaine (0.3 to 1 microM) are particularly effective in potentiating the action of 5-hydroxytryptamine.
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Vollum Institute, Oregon Health Sciences University, Portland 97201.
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D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012686:Septal Nuclei / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012701:Serotonin; D013469:Sulpiride; D003042:Cocaine; D004298:Dopamine