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.