Depolarization inactivation of dopamine neurons: an artifact?
A widely accepted theory postulates that, in rats, chronic treatment with neuroleptics causes the depolarization inactivation of the majority of midbrain dopamine (DA) neurons. The present study was aimed to verify whether general anesthesia and/or other factors might contribute to the depolarization inactivation of A9 and A10 DA neurons. To investigate on the possible role played by DA receptor subtypes, three representatives DA antagonists were used: haloperidol (a mixed D1/D2), (-)-sulpiride (a selective D2) and SCH 23390 (a selective D1). In agreement with previous studies, where neuronal sampling was carried out in animals under chloral hydrate anesthesia, chronic treatment with haloperidol (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, when neuronal sampling was performed in unanesthetized rats, the single administration of haloperidol, (-)-sulpiride, or SCH 23390 (0.5, 25, and 0.3 mg/kg respectively 2-3 hr beforehand) increased the number of spontaneously active A9 and A10 DA neurons and their firing rate, whereas the chronic administration of these drugs (daily for 21-28 d) failed 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 chronic haloperidol or (-)-sulpiride. However, the inhibitory effect was potentiated 24 hr after the last administration of the chronic regimen with these neuroleptics, but it was not influenced by either acute or chronic treatment with SCH 23390.(ABSTRACT TRUNCATED AT 250 WORDS)
Mereu
G
G
Department of Experimental Biology, University of Cagliari, Italy.
Lilliu
V
V
Vargiu
P
P
Muntoni
A L
AL
Diana
M
M
Gessa
G L
GL
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology; D016477:Artifacts; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D014150:Antipsychotic Agents; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine