Behavioral deficits induced by low doses of apomorphine in rats: evidence for a motivational and cognitive dysfunction which discriminates among neuroleptic drugs.
In order to further assess the alterations (motor, motivational or cognitive) that might underlie animal behavioral deficits associated with a reduced dopamine transmission, the effects of apomorphine at doses thought to stimulate dopaminergic autoreceptors were studied on rat operant behavior. Apomorphine (30 micrograms/kg SC) decreased the number of food rewards obtained, when rats trained on a continuous reinforced schedule were shifted to schedules of fixed ratio higher than 2:FR3, FR4, and FR8. In rats shifted to a FR4 schedule, apomorphine (7.5, 15, 30, 60 micrograms/kg SC) dose-relatedly reduced the number of rewards obtained. In rats subjected to previous extinction sessions, apomorphine (30 micrograms/kg) did not affect lever pressing reinstated on presentation of primary reinforcers but inhibited responding renewed on presentation of secondary reinforcers. Under a FR(3 + 1) schedule where the last (rewarded) response was distinct from the initial (non-rewarded) responses, the detrimental effect of apomorphine on response rates was considerably weaker than under a conventional FR4 schedule. The reward deficits caused by apomorphine under the FR4 schedule were dose-dependently and completely reversed by amisulpride (0.125, 0.25, 0.5, 1 and 2 mg/kg), pimozide (0.125 mg/kg), sulpiride (8, 16, 32 and 64 mg/kg), but not by conventional neuroleptics (namely chlorpromazine, fluphenazine, haloperidol, metoclopramide and thioridazine). It is suggested that behavioral deficits associated with a reduced dopamine transmission such as that caused by low doses of apomorphine involve motivational and cognitive dysfunctions rather than motor impairments. In account of its differential sensitivity to neuroleptic drugs, apomorphine-induced deficit might have some relevance for a further delineation of the mechanisms of action of these compounds.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000502:physiology; D008297:Male; D009042:Motivation / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012054:Reinforcement, Psychology / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D014150:Antipsychotic Agents; D001058:Apomorphine; D004298:Dopamine