Enhancement of dopamine actions on rat nucleus accumbens neurones in vitro after methamphetamine pre‐treatment.

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Abstract
1. Intracellular recordings were made from the nucleus accumbens neurons in brain slices from rats previously treated with saline or methamphetamine. 2. In neurones from both methamphetamine- and saline (control)-treated rats, dopamine (0.1 mM) produced three types of responses: a biphasic response consisting of an initial hyperpolarization followed by a depolarization, a monophasic hyperpolarization and a simple depolarization. 3. Haloperidol (1 microM) reversibly suppressed both responses to dopamine; (-)-sulpiride (1 microM) selectively abolished the depolarization and prolonged the hyperpolarization. Forskolin (10 microM) and dibutyryl adenosine 3',5'-cyclic monophosphate (1 mM) mimicked the hyperpolarization. Both of the latter two substances were more effective in neurones from methamphetamine-treated rats than in neurones from control rats. 4. In slices from methamphetamine-treated rats, the dose-response curve for the dopamine hyperpolarization was shifted to the left of that seen in neurones from control rats by a factor of approximately 100. The dose-response curve for the dopamine depolarization was shifted to the right about 10-fold in neurones from rats treated with methamphetamine. 5. In slices from control rats, dopamine (less than or equal to 0.1 mM) and methamphetamine (less than or equal to 1 microM) had no effect on the EPSPs evoked by focal electrical stimulation of the periaccumbens regions: dopamine (greater than or equal to 10 nM) and methamphetamine (1 microM) markedly depressed the EPSPs in slices from methamphetamine-treated rats. Depolarizations evoked by application of exogenous glutamate were unaffected by dopamine (less than 5 microM). 6. In slices from methamphetamine-treated rats, dopamine (greater than or equal to 10 nM), forskolin (greater than or equal to 1 microM) and dibutyryl adenosine 3',5'-cyclic monophosphate (1 mM) depressed Ca2+-dependent spikes as well as the EPSPs. Haloperidol (1 microM) completely reversed the depressions of the EPSPs and Ca2+-dependent spikes by dopamine, while (-)-sulpiride (1 microM) was only partially effective. 7. These results indicate that chronic methamphetamine administration leads to enhancement of the actions of dopamine at D1 receptors located on glutamate and/or aspartate nerve terminals and of the dopamine hyperpolarization of principal neurones, which is also mediated by D1 receptors.

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