enkephalin--ala(2)-mephe(4)-gly(5)- and Bulimia

Neuropeptides and peptide hormones affect food-directed motivation, in part, through actions on brain regions associated with reward processing. For instance, previous reports have shown that stimulating glucagon-like peptide-1 (GLP-1) receptors in the nucleus accumbens (NAc), an area that directs motivational processes towards food and drugs of abuse, has an anorectic effect. In contrast, µ-opioid receptor activation of the NAc increases feeding, particularly on highly palatable diets. While both neurotransmitters act within the NAc to impact food intake, it is not clear if and how they might interact to affect feeding. Therefore, these experiments tested the effects of NAc injections of the GLP-1 receptor agonist Exendin 4 (EX4) or antagonist Exendin 9 (EX9) on the consumption of a sweetened fat diet, with and without simultaneous µ-opioid receptor stimulation. Male Sprague-Dawley rats (n = 8/group, EX4 or EX9) underwent surgery to place bilateral cannula above the NAc core. After recovery, animals were tested following NAc injections of saline or the µ-opioid agonist [D-Ala, N-MePhe, Gly-ol]-enkephalin (DAMGO) (0.025 µg/side), combined with varying doses of EX4 (0, 0.05, or 0.10 µg/side) or EX9 (0, 2.5, 5.0 µg/side), counterbalanced across 6 testing days. Food and water intake, along with locomotor activity, was monitored for 2 h. Mu-opioid receptor stimulation significantly increased feeding, and this effect was reduced by GLP-1 receptor stimulation. In contrast, GLP-1 antagonism with EX9 altered the dynamics of DAMGO-induced binge-like feeding, extending µ-opioid-induced binging, and increasing food consumption. These findings are the first to demonstrate an interaction between NAc µ-opioid and GLP-1 receptors on palatable food intake.

Topics: Animals; Bulimia; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Exenatide; Feeding Behavior; Glucagon-Like Peptide-1 Receptor; Male; Neurotransmitter Agents; Nucleus Accumbens; Peptide Fragments; Rats; Receptors, Opioid, mu

Endogenous opioid peptides within the nucleus accumbens are thought to mediate the hedonic aspects of food intake, particularly foods such as fat and sugar. In view of evidence that the amygdala also regulates positive affect, we hypothesized this brain region participates in the control of opioid-mediated food intake. The robust increase in the intake of fat following intra-accumbens administration of the mu-opioid agonist D-Ala2,Nme-Phe4,Glyol5-enkephalin (DAMGO) was completely blocked by concurrent temporary inactivation (muscimol, GABA(A) agonist) of either the basolateral or central nucleus of the amygdala. In summary, we demonstrate that amygdala inactivation prevents the intra-accumbens opioid induced "binge" eating of fat, possibly through reducing the hedonic properties of high-fat palatable food.

Topics: Amygdala; Analgesics, Opioid; Analysis of Variance; Animals; Behavior, Animal; Bulimia; Drug Interactions; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Fats; Feeding Behavior; GABA Agonists; Male; Microinjections; Motor Activity; Muscimol; Narcotics; Neural Networks, Computer; Rats; Rats, Sprague-Dawley; Time Factors