Profile of the selective dopamine D-2 receptor agonist N-0437: Its effects on palatability- and deprivation-induced feeding, and operant responding for food

Abstract

N-0437 is a potent and highly selective dopamine D-2 receptor agonist, which has been used in the present series of experiments to investigate its potential anorectic properties. In doses of 0.3–3.0 mg/kg (IP), N-0437 significantly reduced consumption of a sweetened palatable mash in nondeprived mice (minimal effective dose, 0.3 mg/kg) and rats (minimal effective dose, 0.56 mg/kg). Reductions in food intake were also produced in rats by the less potent, but selective, D-2 agonist RU 24213 (effective at 10.0 mg/kg), and by d-amphetamine (1.0 and 3.0 mg/kg). The anorectic effect of N-0437 (1.0 mg/kg) was completely antagonized by the selective D-2 antagonist, YM-09151-2 (0.01 mg/kg). Over a series of 10 injections, N-0437 (1.0 mg/kg) maintained its effect to reduce palatable food intake. In food-deprived rats, N-0437 (0.3–3.0 mg/kg, IP) also reduced consumption of standard laboratory food, and dose-dependently reduced operant responding for food under a FR8 schedule of reinforcement. The results of the experiments are discussed in terms of a possible direct effect to reduce feeding responses resulting from stimulation of postsynaptic dopamine D-2 receptors.