Effect of antipsychotic drugs and selective dopaminergic antagonists on dopamine-induced facilitatory activity in prelimbic cortical pyramidal neurons. An in vitro study

Intracellular recordings were obtained from 119 pyramidal neurons localized in prelimbic cortex, five in the dorsal cingulate cortex, one in the infra limbic cortex, one in the border of prelimbic and cingulate cortex and two in the border of prelimbic and infralimbic cortex. The passive membrane pro perties of these pyramidal neurons (i.e. resting membrane potential, input membrane resistance, shape of the tetrodotoxin-sensitive action potentials, spike frequency adaptation with a prominent postspike afterhyperpolarizati on, tetrodotoxin-sensitive inward rectification in the depolarizing directi on and the absence of bursting) suggested that they resembled regular spiki ng or intrinsically bursting pyramidal neurons. Bath application of dopamin e (EC50 of 1.8 mu M) produced a reversible facilitatory effect on all 119 p yramidal neurons localized in the middle layer of the prelimbic cortex. No consistent change in membrane potential was detected during the application of dopamine. No effect of dopamine was noted on the nine pyramidal neurons that were not localized in the prelimbic cortex. The facilitatory effect o f dopamine in prelimbic cortex was concentration dependently antagonized by haloperidol, risperidone, quetiapine, clozapine and by the selective D-4 d opaminergic receptor antagonist L-745,870, but not by the selective D2/D3 d opaminergic receptor antagonist (-)-sulpiride. (+)-SCH 23390, which is a se lective D-1/D-5 dopamine receptor antagonist, produced, similarly to dopami ne, a facilitatory effect per se, and an additive effect when co-administer ed with dopamine. These results provide evidence that dopamine has a facilitatory effect spec ifically on pyramidal neurons localized in the middle layer of prelimbic co rtex. Antipsychotic drugs and L-745,870 block this effect of dopamine. (C) 1999 IBRO. Published by Elsevier Science Ltd.