Neural substrates of fear-induced hypophagia in male and female rats.

Cessation of eating under fear is an adaptive response that aids survival by prioritizing the expression of defensive behaviors over feeding behavior. However, this response can become maladaptive when persistent. Thus, accurate mediation of the competition between fear and feeding is important in health and disease; yet, the underlying neural substrates are largely unknown. The current study identified brain regions that were recruited when a fear cue inhibited feeding in male and female rats. We used a previously established behavioral paradigm to elicit hypophagia with a conditioned cue for footshocks, and Fos imaging to map activation patterns during this behavior. We found that distinct patterns of recruitment were associated with feeding and fear expression, and that these patterns were similar in males and females except within the medial prefrontal cortex (mPFC). In both sexes, food consumption was associated with activation of cell groups in the central amygdalar nucleus, hypothalamus, and dorsal vagal complex, and exposure to food cues was associated with activation of the anterior basolateral amygdalar nucleus. In contrast, fear expression was associated with activation of the lateral and posterior basomedial amygdalar nuclei. Interestingly, selective recruitment of the mPFC in females, but not in males, was associated with both feeding and freezing behavior, suggesting sex differences in the neuronal processing underlying the competition between feeding and fear. This study provided the first evidence of the neural network mediating fear-induced hypophagia, and important functional activation maps for future interrogation of the underlying neural substrates.

Activation patterns of vasopressinergic and oxytocinergic brain regions following social play exposure in juvenile male and female rats.

Social play is a highly rewarding and motivated behavior predominately displayed by juveniles and expressed by nearly all mammalian species. Prior work suggested that the vasopressin (AVP) and oxytocin (OT) systems can regulate the expression of social play in sex-specific ways. Here we investigated whether there are sex differences in the recruitment of vasopressinergic and oxytocinergic brain regions following social play exposure in juvenile rats. Single-housed rats were allowed to play, in their home cage, with an age- and sex-matched unfamiliar conspecific for 10 min, or received similar handling but no partner. Double-labeled fluorescent immunohistochemistry for Fos and either AVP or OT was completed in adjacent series of tissue to determine recruitment of AVP- and OT-immunoreactive neurons in response to social play. Exposure to social play did not increase recruitment of AVP or OT neurons in the supraoptic (SO) or paraventricular (PVH) hypothalamic nuclei of either sex compared to the no-play control condition. Interestingly, there was a robust sex difference in SO recruitment, irrespective of social play condition, with males exhibiting twice the recruitment of SO-AVP and SO-OT neurons compared to females. Lastly, exposure to social play increased recruitment of the posterior bed nuclei of the stria terminalis (pBST) and the posterodorsal medial amygdalar nucleus (MEApd) compared to the no-play control condition, and this effect was most pronounced in females. Our findings revealed sex differences in the recruitment of brain regions (i) independent of play condition (i.e., SO) possibly representing a sex difference in the baseline levels of AVP and OT signaling required for typical functioning and (ii) specific to play condition (i.e., pBST, MEApd). In sum, this study provides further evidence that the neural substrates underlying social play behavior are sex-specific. This article is protected by copyright. All rights reserved.

Selective Fos induction in hypothalamic orexin/hypocretin, but not melanin-concentrating hormone neurons, by a learned food-cue that stimulates feeding in sated rats.

Associative learning can enable cues from the environment to stimulate feeding in the absence of physiological hunger. How learned cues are integrated with the homeostatic regulatory system is unknown. Here we examined whether the underlying mechanism involves the hypothalamic orexigenic neuropeptide regulators orexin/hypocretin (ORX) and melanin-concentrating hormone (MCH). We used a Pavlovian conditioning procedure to train food-restricted rats to associate a discrete cue, a tone, with food pellets distinct from their regular lab chow diet. Rats in the conditioned group (Paired) received presentations of a tone immediately prior to food delivery, while the rats in the control group (Unpaired) received random presentations of the same number of tones and food pellets. After conditioning rats were allowed ad libitum access to lab chow for at least 10days before testing. At test sated rats were presented with the tones in their home cages, and then one group was allowed to consume food pellets, while another group was left undisturbed until sacrifice for Fos induction analysis. The tone cue stimulated food consumption in this setting; rats in the Paired group consumed larger amounts of food pellets than rats in the Unpaired group. To examine Fos induction we processed the brain tissue using fluorescent immunohistochemistry methods for combined detection of Fos and characterization of ORX and MCH neurons. We found a greater percentage of ORX and Fos double-labeled neurons in the Paired compared to the Unpaired condition, specifically in the perifornical area. In contrast, there were very few MCH neurons with Fos induction in both the Paired and Unpaired conditions. Thus, the food-cue selectively induced Fos in ORX but not in MCH neurons. These results suggest a role for ORX in cue-induced feeding that occurs in the absence of physiological hunger.