Characteristics of feeding induced by the serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT)

Abstract

The effects of the putative serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on food intake in freely-feeding and food deprived rats were examined. In freely-feeding rats, low doses of 8-OH-DPAT (15–60 μg/kg) significantly increased food intake without affecting drinking, grooming, rearing or locomotion. Higher drug doses (125–4000 μg/kg) also produced feeding and caused locomotor stimulation and serotonin-related stereotyped behaviour (i.e., forepaw padding, headweaving, wet dog shakes, flat body posture). When feeding and stereotypy were observed concurrently, response competition was evident and feeding behaviour was fragmented into numerous short eating bouts. As drug-induced stereotypy declined with time, this fragmented pattern of eating was succeeded by long bouts of eating which were similar to those observed at doses of 15–60 μg/kg 8-OH-DPAT. In 24 hr food deprived rats, low doses of 8-OH-DPAT had no effect on food intake. However, high doses of 8-OH-DPAT (250–4000 μg/kg) decreased feeding in food deprived animals, an effect which was probably secondary to the induction of stereotypy. It is proposed that the behavioural effects of 8-OH-DPAT may be explained by a dual effect on brain serotonergic mechanisms, which is dose dependent. Thus, low doses of the drug may preferentially activate inhibitory presynaptic serotonin receptors (autoreceptors), decrease serotonin metabolism and thereby increase feeding. In contrast, high doses of 8-OH-DPAT appear to stimulate postsynaptic serotonin receptors and thus produce stereotypy. Alternatively, it is possible that 8-OH-DPAT may elicit feeding by postsynaptic serotonin receptor blockade.