Performance deficit induced by low doses of dopamine agonists in rats. Toward a model for approaching the neurobiology of negative schizophrenic symptomatology?
In searching for reliable animal models of negative schizophrenic symptomatology, we considered the possibility that a deficient response to rewarding stimuli might be the basis for some features of the disease. Apomorphine (0.015 and 0.03 mg/kg) and 3-PPP (1 mg/kg) caused such a reward deficit when rats were shifted from continuous reinforcement to a fixed ratio (FR4) schedule of food delivery. Further experiments indicated that this effect could be accounted for by a decreased ability of secondary reinforcers to sustain responses, rather than by motor impairment, appetite loss, or reduced reward value of the food. If this deficit is due to decreased dopaminergic transmission produced by low doses of dopamine agonists, our model might suggest that some symptoms of schizophrenia (anhedonia for instance) are not incompatible with deficient dopaminergic transmission. Low to moderate doses of sulpiride, amisulpride, pimozide, and pipotiazine, but not fluphenazine, metoclopramide, haloperidol, thioridazine, and chlorpromazine, reversed the apomorphine-induced reward deficit. Although any extrapolation from animal data requires caution, it may be tentatively proposed that only some neuroleptics, at dosages insufficient to block dopamine transmission postsynaptically, can be effective in reducing negative schizophrenic symptoms.
Carnoy
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Soubrie
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Puech
A J
AJ
Simon
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D000077582:Amisulpride; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D010640:Phenothiazines / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology / Q000187:drug effects; D012559:Schizophrenia / Q000503:physiopathology; D012565:Schizophrenic Psychology; D013469:Sulpiride / Q000031:analogs & derivatives / Q000494:pharmacology
D014150:Antipsychotic Agents; D010640:Phenothiazines; D010880:Piperidines; D011954:Receptors, Dopamine; D010868:Pimozide; D013469:Sulpiride; D000077582:Amisulpride; C026539:preclamol; D001058:Apomorphine