Chronic administration of l-sulpiride at low doses reduces A10 but not A9 somatodentritic dopamine autoreceptor sensitivity.
The effect of chronic treatment (twice daily for 21 days) with low doses of l-sulpiride (2 mg/kg i.p.) on the apomorphine-induced inhibition of A10 and A9 dopaminergic neurons was compared with the effect of chronic administration of the classic antidepressant desipramine (20 mg/kg i.p. daily for 21 days). Intravenous administration of apomorphine (0.01-0.04 mg/kg), to rats treated chronically with l-sulpiride, produced a reduction of the spontaneous firing rate of A9 dopaminergic neurons not significantly different from that observed in control (saline-treated) rats. In contrast, apomorphine at the same doses was more potent in inhibiting A10 firing in control rats than in l-sulpiride-treated subjects. On the other hand, desipramine-treated rats were found normosensitive (as compared to saline-treated rats) to the inhibitory properties of apomorphine in both A9 and A10 dopaminergic neurons. It is suggested that chronic l-sulpiride-induced reduction of autoreceptor sensitivity in the A10 region may contribute to its clinical antidepressant effect.
Diana
M
M
Department of Drug Sciences, University of Sassari, Italy.
Muntoni
A L
AL
Pistis
M
M
Collu
M
M
Forgione
A
A
Gessa
G L
GL
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013469:Sulpiride / Q000008:administration & dosage* / Q000494:pharmacology
D011954:Receptors, Dopamine; D013469:Sulpiride; D004298:Dopamine