RADIOFREQUENCY LESIONS OF THE PVN FAIL TO MODIFY THE EFFECTS OF SEROTONERGIC DRUGS ON FOOD-INTAKE

PaSt research has suggested that the paraventricular nucleus (PVN) of the hypothalamus is an important brain site mediating changes in feedi ng induced by drugs that modify 5-hydroxytryptamine (5-HT; serotonin) neurotransmission. To test this possibility, several experiments exami ned the impact of lesions of the PVN on both decreases and increases i n feeding following treatment with 5-HT-acting drugs. Rats with free a ccess to standard lab chow were given access also to a wet mash diet f or 1 h each day. When intakes of this diet had stabilised, rats were d ivided into two groups: one group received bilateral radiofrequency le sions of the PVN, the other served as a sham-operated control group. T he PVN-lesioned group consumed more lab chow and gained significantly more weight over a 10-week period than the control group. Clonidine st imulated feeding in the sham-operated group, but did not do so in the lesioned group. These findings confirmed that the PVN lesions disrupte d the control Of food intake, as well as body weight regulation. The i ndirect 5-HT agoniStS D-fenfluramine (0.63, 1.25 and 2.5 mg/kg) and fl uoxetine (2.5, 5 and 10 mg/kg), and the 5-HT1 agonist 1-(m-trifluorome thylphenyl)piperazine (TFMPP, 0.63, 1.25 and 2.5 mg/kg) dose dependent ly reduced the intake of the wet mash diet in sham-operated animals. T his action was not modified by the PVN lesions. The highest doses of D -fenfluramine and fluoxetine also suppressed intake of chow over the 2 3-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-propylam ino)tetralin (8-OH-DPAT, 62.5, 125 and 250 mug/kg) stimulated the inta ke of chow over a 2-h period, and this effect was observed in both sha m-operated and lesioned rats. Thus, PVN lesions failed to modify eithe r the feeding suppressant or stimulant actions of drugs that alter 5-H T neurotransmission. These results demonstrate that the PVN is not a c ritical site mediating the effects of peripherally injected serotonerg ic drugs on feeding behaviour.