D-Fenfluramine and lorcaserin inhibit the binge-like feeding induced by mu-opioid receptor stimulation of the nucleus accumbens in the rat

摘要

Multiple laboratories have shown that the stimulation of mu-opioid receptors in the nucleus accumbens (NAcc) powerfully increases intake of palatable and high-fat diets. Separate studies have demonstrated that serotonin agonists advance satiety processes, and several serotonin-targeting agents have been prescribed to promote weight loss. However, it is unknown if serotonin signaling can modulate the increased feeding elicited by activation of NAcc mu-opioid receptors. These experiments assessed the effects of systemic treatments with the serotonin agonists D-fenfluramine and lorcaserin on the binge-like feeding induced by mu-opioid receptor stimulation of the NAcc in Sprague-Dawley rats. Consistent with previous reports, stimulation of NAcc mu-opioid receptors (with 0.025 mu g/0.5 mu l/side DAMGO) significantly increased consumption of high-fat vegetable shortening, and systemic treatment with D-fenfluramine and lorcaserin dose-dependently decreased intake. Interestingly, D-fenfluramine and lorcaserin reversed the binge-like feeding observed following stimulation of NAcc mu-opioid receptors. Both serotonergic drugs also attenuated the increases of ambulation observed following administration of DAMGO in the NAcc. These data demonstrate that serotonergic anorectics, in addition to their known role in advancing satiety processes during normal feeding, can also inhibit the binge-like feeding that is elicited by activation of mu-opioid receptors within the ventral striatum.