SCH 23390 blocks drug-conditioned place-preference and place-aversion: anhedonia (lack of reward) or apathy (lack of motivation) after dopamine-receptor blockade?
The influence of the D1 antagonist SCH 23390 on the motivational properties of rewarding (morphine, nicotine and diazepam) and aversive (naloxone, phencyclidine and picrotoxin) drugs was studied in the rat in a two-compartment place-conditioning paradigm, which included a pre-conditioning test for spontaneous place-preference. The specific D1 dopamine-receptor antagonist SCH 23390 (0.05 mg/kg SC), paired with both compartments or, separately, with the preferred or with the non-preferred compartment, failed to affect the spontaneous unconditioned preference of the animal. Pairing of morphine (1.0 mg/kg SC), nicotine (0.6 mg/kg SC) or diazepam (1.0 mg/kg IP) with the less preferred compartment induced significant preference for that compartment. Pairing of SCH 23390 (0.05 mg/kg SC) with both compartments completely blocked the place-preference induced by morphine, nicotine and diazepam. Naloxone (0.8 mg/kg SC), phencyclidine (2.5 mg/kg SC) or picrotoxin (2.0 mg/kg IP) paired with the preferred compartment elicited place-aversion. Pairing of SCH 23390 (0.05 mg/kg SC) with both compartments abolished also the place-aversion induced by naloxone, phencyclidine and picrotoxin. The results indicate that blockade of dopamine transmission blocks the motivational properties of rewarding as well as aversive stimuli. It is suggested that neuroleptics rather than simply blocking the rewarding impact of positive reinforcers (anhedonia, lack of pleasure) exert a more general influence on conditioned behaviour by blocking the affective impact of negative as well as positive reinforcers (apathy, lack of motivation).
Acquas
E
E
Institute of Experimental Pharmacology and Toxicology, University of Cagliari, Italy.
Carboni
E
E
Leone
P
P
Di Chiara
G
G
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology*; D002755:Choice Behavior / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009042:Motivation; D009270:Naloxone / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*
D014150:Antipsychotic Agents; D001552:Benzazepines; D003975:Diazepam; D009020:Morphine; D009270:Naloxone; D009538:Nicotine; D010622:Phencyclidine; D010852:Picrotoxin; D011954:Receptors, Dopamine