Microstructural analysis of the anorectic effect of N-0437, a highly selective dopamine D2 agonist

Drug actions, mediated by dopamine D2 receptors, have been shown to reduce food consumption in rodents. The present study used a microstructural approach to feeding responses to determine the behavioural changes which underlie the anorectic effect of a selective D2 agonist, N-0437. Non-deprived male rats were trained to consume a palatable, sweetened mash in a 30 min test under familiar test conditions. N-0437 (1.0 and 3.0 mg/kg) significantly reduced food intake, but had no effect on the duration of feeding, the duration and frequency of feeding bouts, or on the time course of feeding. Its anorectic effect depended upon a selective reduction in the rate of eating. Microstructural analysis of other behavioural changes which followed treatments with N-0437 indicated that, at 0.3 mg/kg, the drug may have selective dopamine autoreceptor activity, but at 1.0 and 3.0 mg/kg it acts postsynaptically at D2 receptors. The results show that the anorectic effects of N-0437 can be clearly distinguished from the effects of psychomotor stimulants like D-amphetamine or cocaine, but they overlap in part with the effect of the mixed D1/D2 agonist, apomorphine. The results are discussed in relation to a proposed D2 receptor-mediation of one component of the behavioural changes that underlie feeding satiation.