Convergent, not serial, striatal and pallidal circuits regulate opioid-induced food intake

Abstract

Mu opioid receptor (MOR) signaling in the nucleus accumbens (NAcc) elicits marked increases in the consumption of palatable tastants. However, the mechanism and circuitry underlying this effect are not fully understood. Multiple downstream target regions have been implicated in mediating this effect but the role of the ventral pallidum (VP), a primary target of NAcc efferents, has not been well defined. To probe the mechanisms underlying increased consumption, we identified behavioral changes in licking patterns following NAcc MOR stimulation. Because the temporal structure of licking reflects the physiological substrates modulating consumption, these measures provide a useful tool in dissecting the cause of increased consumption following NAcc MOR stimulation. Next, we used a combination of pharmacological inactivation and lesions to define the role of the VP in hyperphagia following infusion of the MOR-specific agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) into the NAcc. In agreement with previous studies, results from lick microstructure analysis suggest that NAcc MOR stimulation augments intake through a palatability-driven mechanism. Our results also demonstrate an important role for the VP in normal feeding behavior: pharmacological inactivation of the VP suppresses baseline and NAcc DAMGO-induced consumption. However, this interaction does not occur through a serial circuit requiring direct projections from the NAcc to the VP. Rather, our results indicate that NAcc and VP circuits converge on a common downstream target that regulates food intake.

μ-Opioid receptor stimulation in the nucleus accumbens elevates fatty tastant intake by increasing palatability and suppressing satiety signals

“…The effects of NAcc DAMGO on lick microstructure during fatty tastant intake were qualitatively similar to those that occurred during sucrose consumption, which we described in a previous study (41). For both sucrose and Intralipid consumption, hyperphagia induced by DAMGO infusion into the NAcc was associated with increased burst duration, suggesting that palatability-related changes play a central role in increasing consumption after NAcc MOR stimulation, independent of the macronutrient content of the solution ingested.…”

“…In some behavioral contexts, DAMGO infusion into the NAcc causes a transient suppression of feeding before subsequent hyperphagia (24,41). However, we found that DAMGOϩsaline infusions resulted in a significant decrease in the latency to begin consumption of high-fat chow [ Fig.…”

“…A series of quantitative analyses were carried out to analyze licking behavior over short and longer behavior epochs. Temporal parameters used in this analysis were based on those used in previous studies (14,39,41). Briefly, bursts of near-continuous licking were defined by interlick intervals (ILIs) Ͻ 1 s in duration.…”

“…These orofacial reactions are correlated with the hedonic impact of tastants (19), suggesting MOR stimulation increases the palatability of the sucrose solution. Third, analysis of lick microstructure indicates that elevated sucrose consumption following infusion of DAMGO into the NAcc occurs through increases in the duration of licking bursts (41). Previous work has shown that burst duration covaries with tastant palatability, with more preferred tastants eliciting longer burst durations (14,39).…”

Endogenous central amygdala mu-opioid receptor signaling promotes sodium appetite in mice

“…However, each opioid receptor subtype is broadly expressed throughout a multitude of brain regions (13,14), and therefore characterizing the precise opioidergic circuitries that contribute to sodium appetite is an important and ongoing focus of research. Studies in which exogenous opioid receptor agonists are infused into local regions of rat brain have proven informative and, for example, have demonstrated that increased MOR signaling within both the nucleus accumbens and ventral pallidum enhances the hedonic palatability of NaCl (15). However, experiments such as these fail to determine whether such mechanisms act endogenously and are physiologically relevant during sodium deficiency.…”