Effects of amperozide and tiospirone, atypical antipsychotic 5-HT2 drugs, on food-reinforced behavior in rats.
Amperozide (AMPZ) is a 5-HT2 receptor antagonist that can decrease consumption of ethanol and prevent cocaine conditioning of a place preference. Tiospirone (TSP) is a 5-HT2 receptor antagonist with affinity for D2, 5-HT1a, and 5-HT7, and sigma receptors, which can decrease consumption of ethanol while increasing food intake. Both drugs were tested for inhibition of food reinforced bar-pressing behavior. Fasted Sprague-Dawley male rats were trained daily on a 15-min FR-5 schedule. After response rates stabilized, each rat in one group received a 60-min pretreatment s.c. with saline, 0.25,0.75, or 2.5 microlmol/kg of AMPZ (injections were twice per week and counterbalanced). Each rat in a second group received a 60-min pretreatment with saline, 0.1,0.3, or 1.0 micromol/kg of TSP. The dose of 2.5 micromol/kg of AMPZ reduced the number of food reinforcements by 21% from saline. The effect was due to a greater decline in bar pressing during the last 5-min block. TSP, 0.3 and 1.0 micromol/kg, significantly reduced the number of reinforcements by 45 and 94% from saline, respectively. In a study of catalepsy, TSP at 0.3 and 1.0 micromol/kg produced akinesia and catalepsy, respectively. Our results indicate that AMPZ-induced reduction of alcohol intake is not due to a nonspecific effect on reward, but the akinetic effects of TSP masks whether or not it has effects on reward.
Arolfo
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MP
Department of Pharmacology and Center for Alcohol and Drug Abuse Studies, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
McMillen
B A
BA
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001070:Appetitive Behavior / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D008032:Limbic System / Q000187:drug effects; D008297:Male; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology*
D014150:Antipsychotic Agents; D010879:Piperazines; D011619:Psychotropic Drugs; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013141:Spiro Compounds; C049058:amperozide; C042709:tiospirone