A comparison of the effects of the 5-HT1 agonists TFMPP and RU 24969 on feeding following peripheral or medial hypothalamic injection

Experiments were conducted to compare the food intake suppressant effects of the 5-hydroxytryptamine (5-HT)1 agonists 1-3-trifluoromethylphenylpiperazine hydrochloride (TFMPP) and 5-methoxy-3-(1,2,3,6-tetrahydropyridinyl)1H indole (RU 24969) following either peripheral or medial hypothalamic injections. The effects of these manipulations were examined in 3 different paradigms involving the stimulation of feeding by: (1) infusion of 25 nmol noradrenaline (NA) into the medial hypothalamus, (2) adaptation to a 20 h food deprivation schedule, and (3) the presentation of a palatable wet mash diet for 1 h each day to ad libitum-fed rats. In all 3 paradigms TFMPP and RU 24969 (0.31-5 mg/kg, i.p.) induced dose-dependent reductions of food intake. Both drugs were somewhat less potent at inhibiting feeding that resulted from food deprivation. In contrast to these results medial hypothalamic infusion of TFMPP or RU 24969 (12.5-50 nmol) failed to affect food intake in any of the 3 tests. This occurred in spite of the fact that both 5-HT (12.5-50 nmol) and fluoxetine (12.5-50 nmol) mildly attenuated the feeding that resulted from NA infusion into the same site. The results provide clear evidence that the food intake suppressant effects of peripherally injected TFMPP and RU 24969 are not mediated in the medial hypothalamus. They also suggest that even though manipulations of serotonergic function within the medial hypothalamus can alter food intake, this probably does not involve selective activation of 5-HT1C and/or 5-HT1B receptors.