Limited cheese intake reduces HPA axis and behavioral stress responses in male rats.

Eating palatable foods reduces behavioral and hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress - an idea referred to by the colloquial term "comfort" food. To study the underlying stress-relieving mechanisms of palatable foods, we previously developed a paradigm of limited sucrose feeding in which male rats are given twice-daily access to a small amount of sucrose drink and subsequently have reduced stress responses. Prior research in humans and rodents implicates high dietary sugars/carbohydrates with reduced stress responsivity. However, it is not clear whether the stress-relieving effects of the limited sucrose paradigm depend upon its macronutrient content. To test this idea, the current work measures stress responses in male rats following the limited intermittent intake of cheese - a highly palatable food that is low in sugar and other carbohydrates. The data show that a history of limited cheese intake (LCI) reduced HPA axis responses to acute psychological (restraint) and physiological (hypoxia) stressors. LCI also reduced behavioral struggling during restraint, increased sociability during a social interaction test, and increased open arm activity in the elevated plus-maze test. Z-score analyses evaluated the extent to which these behavioral effects extended within and across assays, and indicated that there was an overall reduction in stress-related behaviors following LCI. Finally, LCI increased immunolabeling for FosB/deltaFosB (a protein associated with repeated or chronic neuronal activation) in the nucleus accumbens. These results indicate that palatable foods can provide stress blunting regardless of their sugar/carbohydrate composition, and support the idea that food reward per se contributes to stress relief.

Palatable food access impacts expression of amylin receptor components in the mesocorticolimbic system.

NEW FINDINGS: What is the central question of this study? We tested whether intra-nucleus accumbens core amylin receptor (AmyR) activation suppresses feeding and evaluated whether intake of palatable food influences mesocorticolimbic AmyR expression. What is the main finding and its importance? Intra-nucleus accumbens core AmyR activation reduces food intake in some dietary conditions. We showed that all components of the AmyR are expressed in the prefrontal cortex and central nucleus of the amygdala and demonstrated that access to fat impacts AmyR expression in these and other mesocorticolimbic nuclei. These results suggest that the intake of palatable food might alter amylin signalling in the brain and shed further light onto potential sites of action for amylin. ABSTRACT: Amylin is a pancreas- and brain-derived peptide that acts within the CNS to promote negative energy balance. However, our understanding of the CNS sites of action for amylin remains incomplete. Here, we investigate the effect of amylin receptor (AmyR) activation in the nucleus accumbens core (NAcC) on the intake of bland and palatable foods. Intra-NAcC injection of the AmyR agonist salmon calcitonin or amylin itself in male chow-fed rats had no effect on food intake, meal size or number of meals. However, in chow-fed rats with access to fat solution, although fat intake was not affected by intra-NAcC AmyR activation, subsequent chow intake was suppressed. Given that mesolimbic AmyR activation suppresses energy intake in rats with access to fat solution, we tested whether fat access changes AmyR expression in key mesocorticolimbic nuclei. Fat exposure did not affect NAcC AmyR expression, whereas in the accumbens shell, expression of receptor activity modifying protein (RAMP) 3 was significantly reduced in fat-consuming rats. We show that all components of AmyRs are expressed in the medial prefrontal cortex and central nucleus of the amygdala; fat access significantly reduced expression of calcitonin receptor-A in the central nucleus of the amygdala and RAMP2 in the medial prefrontal cortex. Taken together, these results indicate that intra-NAcC AmyR activation can suppress energy intake and, furthermore, suggest that AmyR signalling in a broader range of mesocorticolimbic sites might have a role in mediating the effects of amylin on food intake and body weight.

Paclitaxel Causes Electrophysiological Changes in the Anterior Cingulate Cortex via Modulation of the γ-Aminobutyric Acid-ergic System.

OBJECTIVE: The aim of this study was to elucidate any electrophysiological changes that may contribute to the development of neuropathic pain during treatment with the anticancer drug paclitaxel, particularly in the γ-aminobutyric acid (GABA) system. MATERIALS AND METHODS: One hundred and eight Sprague-Dawley rats were used (untreated control: 43; vehicle-treated: 21, and paclitaxel-treated: 44). Paclitaxel (8 mg/kg) was administered intraperitoneally on 2 alternate days to induce mechanical allodynia. The rats were sacrificed 7 days after treatment to obtain slices of the anterior cingulate cortex (ACC), a brain region involved in the central processing of pain. Field excitatory postsynaptic potentials (fEPSPs) were recorded in layer II/III of ACC slices, and stimulus-response curves were constructed. The observed effects were pharmacologically characterized by bath application of GABA and appropriate drugs to the slices. RESULTS: The paclitaxel-treated rats developed mechanical allodynia (i.e. reduced withdrawal threshold to mechanical stimuli). Slices from paclitaxel-treated rats produced a significantly higher maximal response (Emax) than those from untreated rats (p < 0.001). Bath application of GABA (0.4 µM) reversed this effect and returned the excitability to a level similar to control. Pretreatment of the slices with the GABAB receptor blocker CGP 55845 (50 µM) increased Emax in slices from untreated rats (p < 0.01) but not from paclitaxel-treated rats. CONCLUSION: In this study, there was a GABA deficit in paclitaxel-treated rats compared to untreated ones. Such a deficit could contribute to the pathophysiology of paclitaxel-induced neuropathic pain (PINP). Thus, the GABAergic system might be a potential therapeutic target for managing PINP.