ACTIONS OF COCAINE ON RAT NUCLEUS ACCUMBENS NEURONS INVITRO

1. Intracellular recordings were made from 103 neurones of the rat nucleus accumbens in vitro. 2. Dopamine (3-100 μM; in sulpiride, 1 μM) hyperpolarized neurones (79%) by acting at D1 receptors: dopamine (3-100 μM; in SCH23390, 1 μM) depolarized neurones (55%) by acting at D2 receptors. 5-Hydroxytryptamine (1-100 μM) depolarized 86% neurones. 3. Both actions of dopamine as well as the effect of 5-hydroxytryptamine were potentiated by cocaine (0.3-30 μM), 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 μM) caused the same dose-ratio whether dopamine depolarizations (D2) or hyperpolarizations (D1) were measured; the dose-ratio ranged from 2 (1 μM) to 50 (30 μM). 5. Responses to 5-hydroxytryptamine were increased more than responses to dopamine; cocaine 1 μM gave a dose-ratio of 13.4 and at 30 μM 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 μM) are particularly effective in potentiating the action of 5-hydroxytryptamine.