Sweetened-Fat Intake Sensitizes Gamma-Aminobutyric Acid—Mediated Feeding Responses Elicited from the Nucleus Accumbens Shell

Abstract

Background There is much interest in exploring whether reward-driven feeding can produce druglike plasticity in the brain. The gamma-aminobutyric acid (GABA) system in the nucleus accumbens (Acb) shell, which modulates hypothalamic feeding systems, is well placed to “usurp” homeostatic control of feeding. Nevertheless, it is unknown whether feeding-induced neuroadaptations occur in this system. Methods Separate groups of ad libitum–maintained rats were exposed to daily bouts of sweetened-fat intake, predator stress, or intra-Acb shell infusions of either d-amphetamine (2 or 10 μg) or the μ-opioid agonist D-[Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO, 2.5 μg), then challenged with intra-Acb shell infusion of the GABAA agonist, muscimol (10 ng). Results Exposure to sweetened fat robustly sensitized muscimol-induced feeding. Sensitization was present 1 week after cessation of the palatable feeding regimen but had abated by 2 weeks. Rats exposed to sweetened fat did not show an altered feeding response to food deprivation. Repeated intra-Acb shell infusions of DAMGO (2.5 μg) also sensitized intra-Acb shell muscimol-driven feeding. However, neither repeated intra-Acb shell d-amphetamine infusions (2 or 10 μg) nor intermittent exposure to an aversive stimulus (predator stress) altered sensitivity to muscimol. Conclusions Palatable feeding engenders hypersensitivity of Acb shell GABA responses; this effect may involve feeding-induced release of opioid peptides. Heightened arousal, aversive experiences, or increased catecholamine transmission alone are insufficient to produce the effect, and a hunger-induced feeding drive is insufficient to reveal the effect. These findings reveal a novel type of food-induced neuroadaptation within the Acb; possible implications for understanding crossover effects between food reward and drug reward are discussed.

Amphetamine acts within the lateral hypothalamic area to elicit affectively neutral arousal and reinstate drug-seeking

“…medial portions of the dorsal hypothalamus. Importantly, the low level and pattern of locomotor activity observed in this study is similar to that seen with spontaneous waking (Berridge and Foote, 1996) and is substantially below levels seen with behaviourally-activating doses of systemically-administered psychostimulants (Kuczenski et al, 1991, 1997; Segal, 1975; Segal and Kuczenski, 1997) or with AMPH infusion into the nucleus accumbens at doses similar to those used in the current studies (Newman et al, 2013; Schildein et al, 1998). No evidence of stereotypy was observed with either unilateral or bilateral AMPH infusions.…”

“…Doses used in the intra-tissue infusion studies were based on previous studies demonstrating this dose range elicited robust waking when infused into the medial septal and medial preoptic areas (Berridge et al, 1999) and locomotor-activating and reinforcing effects when infused into the nucleus accumbens (Carr and White, 1983; Gerdjikov and Beninger, 2005, 2006; Newman et al, 2013; Schildein et al, 1998). For CPP studies, systemic doses were used that have been demonstrated to elicit pronounced arousal-promoting actions in the absence of a strong locomotor activation (Berridge et al, 1999; Berridge and Stalnaker, 2002).…”

Prefrontal Cortical Opioids and Dysregulated Motivation: A Network Hypothesis

“…Nevertheless, this ‘normal’ μ-OR-mediated regulation could progress to dysregulation if μ-OR activation occurs in the context of a faulty efferent network; for example, if the motivational ‘limiter’ function of the circuitry has been compromised and can no longer hold cortically driven responses in check. Recent findings have begun to suggest that exposure to reward-driven feeding engenders adaptations within PFC terminal fields that could, in principle, result in a blunting of the proposed PFC→AcbSh ‘limiter circuit’ [85]. Rats that had gorged daily on sweetened fat displayed a markedly sensitized feeding response to a low-dose intra-AcbSh challenge of the GABA agonist, muscimol.…”

GABA-Mediated Inactivation of Medial Prefrontal and Agranular Insular Cortex in the Rat: Contrasting Effects on Hunger- and Palatability-Driven Feeding

“…On the output side, both the vmPFC and AIC send direct projections to feedingmodulatory hypothalamic regions (Hurley et al, 1991;Floyd et al, 2001). Additionally, vmPFC (and, to a lesser extent, the AIC) sends strong projections to the nucleus accumbens shell (Vertes, 2004;Reynolds and Zahm, 2005), a site at which profound hyperphagia is elicited by GABA or opiate receptor stimulation (Basso and Kelley, 1999;Newman et al, 2013).…”