Radiofrequency lesions of the PVN fail to modify the effects of serotonergic drugs on food intake

Abstract

Past research has suggested that the paraventricular nucleus (PVN) of the hypothalamus is an important brain site mediating changes in feeding induced by drugs that modify 5-hydroxytryptamine (5-HT; serotonin) neurotransmission. To test this possibility, several experiments examined the impact of lesions of the PVN on both decreases and increases in feeding following treatment with 5-HT-acting drugs. Rats with free access to standard lab chow were given access also to a wet mash diet for 1 h each day. When intakes of this diet had stabilised, rats were divided into two groups: one group received bilateral radiofrequency lesions of the PVN, the other served as a sham-operated control group. The PVN-lesioned group consumed more lab chow and gained significantly more weight over a 10-week period than the control group. Clonidine stimulated feeding in the sham-operated group, but did not do so in the lesioned group. These findings confirmed that the PVN lesions disrupted the control of food intake, as well as body weight regulation. The indirect 5-HT agonists d-fenfluramine (0.63, 1.25 and 2.5 mg/kg) and fluoxetine (2.5, 5 and 10 mg/kg ), and the 5-HT1 agonist 1(m-trifluoromethylphenyl)piperazine (TFMPP, 0.63, 1.25 and 2.5 mg/kg) dose dependently reduced the intake of the wet mash diet in sham-operated animals. This action was not modified by the PVN lesions. The highest doses of d-fenfluramine and fluoxetine also suppressed intake of chow over the 23-h period subsequent to the wet mash presentations, but the magnitude of this effect was similar in sham-operated and PVN-lesioned animals. Peripheral injection of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 62.5, 125 and 250 μg/kg) stimulated the intake of chow over a 2-h period, and this effect was observed in both sham-operated and lesioned rats. Thus, PVN lesions failed to modify either the feeding suppressant or stimulant actions of drugs that alter 5-HT neurotransmission. These results demonstrate that the PVN is not a critical site mediating the effects of peripherally injected serotonergic drugs on feeding behaviour. © 1993.