Potentiation by low doses of selected neuroleptics of food-induced conditioned place preference in rats.
Numerous data support the hypothesis that dopamine (DA) plays a crucial role in reward-related processes and in incentive learning in animals and man. The possibility that various neuroleptics exhibiting a high affinity for the dopaminergic D2 (and D3) receptors could reinforce DA transmission was studied using the conditioned place preference paradigm (CPP) in rats. This was done by examining the ability of these compounds to potentiate the reinforcing properties of food in hungry rats subjected to a version of the CPP paradigm which consisted of repeated pairings of food with a single environmental cue, the floor texture of an open field. During the test session when food was no longer available in the open field, the increase in the time spent by drug-free rats on the food-paired texture was assumed to indicate the perceived rewarding value of the food. This time was significantly lengthened when the specific D2 (D3)-receptor antagonists sulpiride (4 mg/kg), amisulpride (0.5, 1 mg/kg) or pimozide (0.03, 0.06 mg/kg) were administered before the food conditioning sessions. Larger doses of these compounds as well as haloperidol, metoclopramide and the non-specific D1-D2 antagonist, chlorpromazine, regardless of the doses tested, did not exhibit this effect, but rather reduced the food-induced CPP, an action usually associated with neuroleptics. The positive effects of amisulpride was reversed by a D1 receptor antagonist, SCH 23390 (0.01 mg/kg). These results suggest that, as with amphetamine (0.5 mg/kg), some D2-specific neuroleptics enhance the incentive value of food in a narrow range of low doses, an effect proposed to reflect a "prohedonic" property.(ABSTRACT TRUNCATED AT 250 WORDS)
Guyon
A
A
INSERM U-302, Département de Pharmacologie, Faculté de Médecine Pitié-Salpêtriére, Paris, France.
Assouly-Besse
F
F
Biala
G
G
Puech
A J
AJ
Thiébot
M H
MH
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D065127:Dopamine D2 Receptor Antagonists; D005502:Food; D005508:Food Deprivation / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D012054:Reinforcement, Psychology; D012201:Reward; D013395:Sucrose / Q000494:pharmacology
D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D013395:Sucrose