DEPOLARIZATION INACTIVATION OF DOPAMINE NEURONS - AN ARTIFACT

A widely accepted theory postulates that, in rats, chronic treatment w ith neuroleptics causes the depolarization inactivation of the majorit y of midbrain dopamine (DA) neurons. The present study was aimed to ve rify whether general anesthesia and/or other factors might contribute to the depolarization inactivation of A9 and A10 DA neurons. To invest igate on the possible role played by DA receptor subtypes, three repre sentatives DA antagonists were used: haloperidol (a mixed D1/D2), (-)- sulpiride (a selective D2) and SCH 23390 (a selective D1). In agreemen t with previous studies, where neuronal sampling was carried out in an imals under chloral hydrate anesthesia, chronic treatment with haloper idol(0.5 mg/kg daily for 21-28 d) produced a profound reduction (about 80%) in the number of spontaneously active A9 DA neurons. However, wh en neuronal sampling was performed in unanesthetized rats, the single administration of haloperidol, (-)-sulpiride, or SCH 23390 (0.5, 25, a nd 0.3 mg/kg respectively 2-3 hr beforehand) increased the number of s pontaneously active A9 and A10 DA neurons and their firing rate, where as the chronic administration of these drugs (daily for 21-28 d) faile d to reduce the number of spontaneously active A9 and A10 DA neurons. The inhibitory effect of apomorphine on the firing rate of A9 and A10 DA neurons was prevented 3-4 hr after the acute or last injection of c hronic haloperidol or (-)-sulpiride. However, the inhibitory effect wa s potentiated 24 hr after the last administration of the chronic regim en with these neuroleptics, but it was not influenced by either acute or chronic treatment with SCH 23390. The results suggest that depolari zation inactivation is likely to be produced as a consequence of neuro leptic-induced hyperexcitability of DA neurons combined with their sti mulation by general anesthetics. Moreover, our study confirms that DA neurons become supersensitive to apomorphine after chronic neuroleptic treatment.