Feeding-modulatory effects of mu-opioids in the medial prefrontal cortex: a review of recent findings and comparison to opioid actions in the nucleus accumbens

Abstract

Rationale Whereas reward-modulatory opioid actions have been intensively studied in subcortical sites such as the nucleus accumbens (Acb), the role of cortical opioid transmission has received comparatively little attention. Objectives To describe recent findings on the motivational actions of opioids in the prefrontal cortex (PFC), emphasizing studies of food motivation and ingestion. PFC-based opioid effects will be compared/contrasted to those elicited from the Acb, to glean possible common functional principles. Finally, the motivational effects of opioids will be placed within a network context involving the PFC, Acb, and hypothalamus. Results Mu-opioid receptor (μ-OR) stimulation in both the Acb and PFC induces eating and enhances food-seeking instrumental behaviors; μ-OR signaling also enhances taste reactivity within a highly circumscribed zone of medial Acb shell. In both the Acb and PFC, opioid-sensitive zones are aligned topographically with the sectors that project to feeding-modulatory zones of the hypothalamus, and intact glutamate transmission in the lateral/perifornical (LH-PeF) hypothalamic areas is required for both Acb- and PFC-driven feeding. Conversely, opioid-mediated feeding responses elicited from the PFC are negatively modulated by AMPA signaling in the Acb shell. Conclusions Opioid signaling in the PFC engages functionally opposed PFC→hypothalamus and PFC→Acb circuits, which respectively drive and limit non-homeostatic feeding, producing a disorganized and ‘fragmented’ pattern of impulsive food-seeking behaviors and hyperactivity. In addition, opioids act directly in the Acb to facilitate food motivation and taste hedonics. Further study of this cortico-striato-hypothalamic circuit, and incorporation of additional opioid-responsive telencephalic structures, could yield insights with translational relevance for eating disorders and obesity.

Optogenetic activation of amygdala projections to nucleus accumbens can arrest conditioned and unconditioned alcohol consummatory behavior

“…It is not clear whether we would have seen similar effects of stimulating other excitatory glutamatergic inputs into the AcbSh although recent studies support a role for multiple inputs, including the prefrontal cortex and the thalamus, in reward seeking and consumption (Britt et al, 2012; Do-Monte et al, 2017; Prado et al, 2016; Selleck and Baldo, 2017; Stuber et al, 2011). For example, Britt et al found that mice will respond for activation of prefrontal, BLA, or hippocampual accumbal inputs (Britt et al, 2012).…”

“…Second, although photoactivation interrupted alcohol drinking, animals continued to interact with the sipper tube during the alcohol drinking test. These within-test dissociations are intriguing and raise important questions about control over the sequence of reward-seeking actions, specifically between approach and “terminal”, consummatory, responses, which are proposed to engage different learning systems (Chang and Smith, 2016; Naeem and White, 2016; Selleck and Baldo, 2017). The findings suggest the interesting possibility that consummatory responses/terminal responses, may be more sensitive to the influence of BLA-AcbSh innervation than more distal actions within the behavioral chain, a possibility awaiting future testing.…”

“…For example, Britt et al found that mice will respond for activation of prefrontal, BLA, or hippocampual accumbal inputs (Britt et al, 2012). The prefrontal cortex has been suggested to be critical for behavior selection and for switching between appetitive and consummatory behavior (c.f.,(Selleck and Baldo, 2017). Additionally, activation of inputs from the paraventricular nucleus of the thalamus during instrumental nosepoking for sucrose decreases nosepoke responding, yet did not reduce ad libitum sucrose consumption (Do-Monte et al, 2017).…”

Predicting personality from network-based resting-state functional connectivity

“…; Allen and DeYoung 2016) and its genetic variation has been also pointed to the opiate system, due to its involvement in the hedonic response to the stimulus (Peciña et al 2006). It is, therefore, possible that the endogenous opioid system via modulation of amygdala and medial prefrontal cortex (Tejeda et al 2015; Selleck and Baldo 2017), most used regions in the connections of Face , mediate both the perception of faces (Martin et al 2006) and the social bonding (Pasternak and Pan 2013). We thus suggest that functional connectivity within the Face network in Men is mostly related to the “Affiliative” aspect of Extraversion.…”

Opioid and nondopamine reward circuitry and state‐dependent mechanisms

“…Additionally, MOP receptors mediate the rewarding properties of other nonopioid drugs of abuse, such as cocaine, nicotine, and ethanol . Furthermore, MOP receptors are involved in natural reward, such as feeding . Feeding was shown to increase endogenous opioid release …”