Cholecystokinin-induced inhibition of dopamine neurotransmission: comparison with chronic haloperidol treatment.
A dose-dependent inhibition of DA release was observed by in vivo electrochemical techniques after acute i.v. injections of CCK8-S (1.0-8.0 micrograms/kg). The threshold dose was 1.0 microgram/kg, and maximum inhibition of release (90%) was obtained with doses of 4 and 8 micrograms/kg. Injections of CCK8-US (4-20 micrograms/kg) had no effect on DA release. Repeated treatment with haloperidol (0.5 mg/kg s.c.) for 21 days produced a 47% inhibition of DA release in the nucleus accumbens. Apomorphine (50 micrograms/kg) reversed the inhibitory effects of both acute injections of CCK8-S and prolonged haloperidol treatment on DA release. In contrast, apomorphine (50 micrograms/kg) administered alone inhibited DA release, presumably via hyperpolarization of DA neurons. The attenuation of DA release by either an acute injection of CCK8-S or repeated treatment with haloperidol is attributed to the induction of depolarization block in mesolimbic DA neurons. These data may be indicative of antipsychotic properties of CCK8-S.
Lane
R F
RF
Blaha
C D
CD
Phillips
A G
AG
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D012686:Septal Nuclei / Q000187:drug effects*; D012844:Sincalide / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*
D011954:Receptors, Dopamine; D006220:Haloperidol; D012844:Sincalide; D001058:Apomorphine; D004298:Dopamine