Contrasting effects of 5-HT3 receptor stimulation of the nucleus accumbens or ventral tegmentum on food intake in the rat.

Abstract Although serotonin (5-HT) signaling is known to regulate food intake and energy homeostasis, the roles of the 5-HT 3 receptor in feeding processes have been elusive. 5-HT 3 receptors are found throughout mesolimbic circuitry that promote feeding not only in response to hunger, but also to the palatable and rewarding properties of food. These experiments examined if stimulation or blockade of the 5-HT 3 receptor of the nucleus accumbens (NAcc) or ventral tegmentum affected food intake in the rat in response to hunger or the presence of a palatable diet. Rats (N = 6–9/group) received bilateral injections of the 5-HT 3 agonist m-chlorophenylbiguanide hydrochloride (mCPBG; at 0.0, 10.0, or 20.0 μg/0.5 μl/side) or the 5-HT 3 antagonist ondansetron hydrochloride (at 0.0, 1.0, 2.0, or 5.0 μg/0.5 μl/side) into either the NAcc or the ventral tegmentum. NAcc 5-HT 3 receptor stimulation significantly increased 2-h food intake in food-deprived animals offered rat chow and in a separate group of unrestricted rats offered a sweetened fat diet. In contrast to the feeding increase seen with NAcc treatments, stimulation of 5-HT 3 receptors of the ventral tegmentum significantly reduced food and water intake in food-restricted animals; reductions of intake in non-restricted rats offered the palatable diet did not approach significance. Blockade of the 5-HT 3 receptor had no effect on feeding in either brain region. These data support a functional role for serotonergic signaling in the mesolimbic pathway on motivated behavior, and demonstrate that 5-HT 3 receptors differentially modulate food consumption in a region-dependent manner.