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.