Pharmacological characterization of high-fat feeding induced by opioid stimulation of the ventral striatum

Abstract

Nucleus accumbens μ-opioid stimulation causes marked increases in the intake of highly palatable foods, such as a high-fat diet. However, to date there has been little examination of how other striatal neurotransmitters may mediate opioid-driven feeding of palatable foodstuffs. In the current study, free feeding rats with bilateral cannulae aimed at the nucleus accumbens received intra-accumbens pretreatment with antagonists for dopamine D-1 (SCH23390; 0 μg or 1 μg/0.5 μl/side), dopamine D-2 (raclopride; 0 μg or 2.0 μg/0.5 μl/side), AMPA (LY293558; 0 μg, 0.01 μg or 0.10 μg/0.5 μl/side), muscarinic (scopolamine 0 μg, 0.1, 1.0, or 10 μg/0.5 μl/side) or nicotinic (mecamylamine; 0 μg, 10 μg/0.5 μl/side) receptors, immediately prior to infusions of the μ-receptor agonist D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO; 0.25 μg/0.5 μl) or vehicle. The effects of these pretreatments on 2 hr fat intake was compared to pretreatment with a general opioid antagonist (naltrexone; 0 μg or 20 μg/0.5 μl/side). DAMGO-induced feeding was unaffected by prior antagonism of dopamine, glutamate, or nicotinic receptors. As expected, naltrexone infusions blocked DAMGO-elicited fat intake. Antagonism of muscarinic acetylcholine receptors reduced feeding in both the DAMGO and vehicle-treated conditions. In an additional experiment, cholinergic receptor stimulation alone did not affect intake of the fat diet, suggesting that nucleus accumbens cholinergic stimulation is insufficient to alter feeding of a highly palatable food. These data suggest that the feeding effects caused by striatal opioid stimulation are independent from or downstream to the actions of dopamine and glutamate signaling, and provide novel insight into the role of striatal acetylcholine on feeding behaviors.