Effects of the opioid antagonist naltrexone on feeding induced by DAMGO in the ventral tegmental area and in the nucleus accumbens shell region in the rat

Abstract

. Effects of the opioid antagonist naltrexone on feeding induced by DAMGO in the ventral tegmental area and in the nucleus accumbens shell region in the rat. Am J Physiol Regul Integr Comp Physiol 285: R999-R1004, 2003. First published August 7, 2003 10.1152/ajpregu.00271. 2003.-The nucleus accumbens shell region (sNAcc) and the ventral tegmental area (VTA) are two major nodes in the mesolimbic dopamine pathway, which mediates reward for various survival behaviors, including feeding. Opioids increase and maintain food intake when injected peripherally and centrally. Opioids in the VTA cause increased release of dopamine in the sNAcc, and when injected into either site, cause an increase in food intake. Animals in this study were double cannulated in the VTA and in the sNAcc and injected with various combinations of naltrexone (NTX) (2.5, 5, and 25 g/side) and Tyr-D-Ala-Gly-(Me)Phe-Gly-ol (DAMGO) (0.1, 0.3, 1, 3, and 5 nmol/side) in both sites. DAMGO was found to dose dependently increase intake to an equal extent when injected into either site. DAMGO-induced increases in food intake when injected into the VTA were blocked to control levels with the highest dose of NTX injected bilaterally into the sNAcc; however, increases in intake when injected into the sNAcc were blocked only partially by the highest dose of NTX injected bilaterally into the VTA. These results indicate opioid-opioid communication between the two sites; however, the communication may be quite indirect, requiring other sites and transmitters to elicit a change in behavior. food intake; mesolimbic; microinjection; reward FOOD INTAKE results from the behavioral output of a diverse network of sites that integrates metabolic, emotional, and hedonic demands for increased or decreased consumption. Several peptides and neurotransmitters are responsible for different aspects of this behavior and appear to exert their effects differently in various brain sites (15). Opioids are thought to prolong intake, particularly of highly palatable foods, but not to initiate intake (9, 10), and this is not based on postabsorptive signals (11, 12). Opioid antagonists have been shown to inhibit intake of highly preferred foods much more robustly than less preferred foods, strengthening the argument that opioids are involved in the response to the quality of the food, rather than to hunger (16,29). Because opioids are also well-known hedonic agents, their actions in brain reward systems have been examined with regard to food intake.The ventral tegmental area (VTA) and the nucleus accumbens shell region (sNAcc) are part of the mesolimbic dopamine (DA) pathway that mediates responses to rewarding stimuli such as drugs of abuse, electrical stimulation, sex, and food intake (8). When opioids bind to their receptors in the VTA, they inhibit GABAergic inhibitory interneurons that synapse on DA cells projecting to the sNAcc. In this way, opioids injected or released into this site increase DA release in the sNAcc. This is thought to be part of the process that maintains f...

Opioid-Dependent Anticipatory Negative Contrast and Binge-Like Eating in Rats with Limited Access to Highly Preferred Food

“…Several previous findings support the hypothesis that mesolimbic opioid receptors modulate behavioral responses to rewarding stimuli, including hedonically driven consumption of preferred foods (Kelley et al, 2002). Nalmefene may have blunted binge-like eating by blocking opioid receptors in the ventral tegmental area, thereby disinhibiting GABAergic inhibitory interneurons that synapse on dopamine neurons and decreasing dopamine release in the shell of the nucleus accumbens (Taber et al, 1998;MacDonald et al, 2003MacDonald et al, , 2004. Nalmefene also might have acted by blocking m-opioid receptors in the nucleus accumbens shell or ventral pallidum (Woolley et al, 2006;Ward et al, 2006), cooperative components of a neurocircuit for amplifying appetitive responses to preferred foods, substances of abuse, and other rewards (Smith and Berridge, 2007;Kelley et al, 2005).…”

Opioid Limbic Circuit for Reward: Interaction between Hedonic Hotspots of Nucleus Accumbens and Ventral Pallidum

“…For example, NAc shell projects directly to the LH, dorsomedial hypothalamus, ventral tegmental area, nucleus of the solitary tract, and central and basolateral amygdala, as well as to VP (Heimer et al, 1991;Zahm, 2000). Furthermore, eating behavior evoked by NAc-DAMGO can be blocked by simultaneous muscimol inactivation or opioid antagonism in LH, ventral tegmentum, or amygdala (MacDonald et al, 2003;Will et al, 2003;Kim et al, 2004;Will et al, 2004;Bodnar et al, 2005). The LH is especially implicated in food intake , and we noted here that DAMGO infusions in the NAc shell also caused increased Fos expression in LH (besides in VP), whereas naloxone in NAc conversely suppressed spontaneous Fos below normal levels in LH (besides in VP).…”

Double Dissociation of Exteroceptive and Interoceptive Feedback Systems in the Orbital and Ventromedial Prefrontal Cortex of Humans

“…Brodmann areas (BAs) are assigned per Price (Öngür et al, 2003), mapped onto the atlas of Talairach and Tournoux (1988). (Korotkova et al, 2003;MacDonald et al, 2003). Recent neuroimaging studies are beginning to show that both VMPFC and VTA/SN are important in human food consumption and obesity (J. V. Pardo, S. A. Sheikh, B. R. Rittberg, and D. E. Adson, unpublished observation), consistent with a role in visceroappetitive/interoceptive processing.…”