Sex differences in motivational responses to dietary fat in Syrian hamsters

Abstract

Women are more likely than men to exhibit motivational disorders (e.g., anhedonia and anxiety) with limited treatment options, and to overconsume high-fat “comfort foods” to improve motivational disruptions. Unfortunately, neurobiological underpinnings for sex differences in motivational disruptions and their responses to dietary fat are poorly understood. To help bridge these fundamental knowledge gaps, we assessed behavioral and neurobiological responses to dietary fat in a hamster model of female-biased motivational lability. Relative to social housing, social separation reduced hedonic drive in a new behavioral assay, the reward investigational preference (RIP) test. Fluoxetine or desipramine treatment for 21, but not 7, days improved RIP test performance. Pharmacologic specificity in this test was shown by non-responsiveness to diazepam, tracazolate, propranolol, or naltrexone. In the anxiety-related feeding/exploration conflict (AFEC) test, social separation worsened latency to eat highly palatable food under anxiogenic conditions, but not in home cages. Social separation also reduced weight gain, food intake, and adiposity while elevating energy expenditure, assessed by caloric efficiency and indirect calorimetry. Furthermore, chronic high-fat feeding improved anhedonic and anxious responses to separation, particularly in females. In the motivation-influencing nucleus accumbens, females, but not males, exhibited a separation-induced anxiety-related decrease in Creb1 mRNA levels and an anhedonia-related decrease in ΔFosb mRNA levels. Consistent with its antidepressant- and anxiolytic-like effects on behavior, high-fat feeding elevated accumbal Creb1 and ΔFosb mRNA levels in females only. Another accumbal reward marker, Tlr4 mRNA, was elevated in females by high-fat feeding. These results show that social separation of hamsters provides a novel model of sex-dependent comorbid anhedonia, anxiety, and anorexia, and implicate accumbal CREB, ΔFosB, and TLR4. Moreover, the results validate a new assay for chronic anti-depressant efficacy.

Mir363-3p improves ischemic stroke outcomes in female but not male rats

“…Only a few gene targets have been rigorously validated by reporter assays and these are shown in Table 2. Overall, mir363-3p appears to targets genes directly or indirectly involved with apoptotic cell death (Li et al, 2016, Wang et al, 2016), and some of these genes display either functional sex differences or are responsive to estrogen (Tsukahara et al, 2006, Tsukahara, 2009, Utge et al, 2010, Sharma et al, 2011, Caliceti et al, 2013, Fan et al, 2014, Zhao et al, 2014, Shannonhouse et al, 2015). Both caspase-3 and -9 play a role in apoptotic cell death, with caspase-9 being an initiator caspase, and caspase-3, an executioner caspase.…”

Fluoxetine disrupts motivation and GABAergic signaling in adolescent female hamsters

“…We have shown previously that fluoxetine is anorexigenic (Wellman, Jones et al 2003) and that reductions in food intake by deprivation or social manipulation are associated with the worsening of motivated behaviors in hamsters (Shannonhouse, Fong et al 2014, Shannonhouse, Grater et al 2015. Therefore, we assessed whether anorexigenic effects of fluoxetine caused the behavioral deficits described above.…”

“…Increases in cumulative reward investigation and reward investigational preference (reward investigation / total investigation x 100) provided indices of hedonic drive. The RIP test is responsive to chronic, but not acute, antidepressant treatment, and unresponsive to non-antidepressant drugs (Shannonhouse, Grater et al 2015).…”

“…Anxiety-related feeding/exploration conflict (AFEC) test. Subjects were assessed as we have described previously (Shannonhouse, Fong et al 2014, Shannonhouse, Grater et al 2015. After transfer of a subject to test cages, graham cracker was presented overhead in a spring-loaded utility clamp.…”

“…RNA extraction. As we have described previously (Shannonhouse, Grater et al 2015), tissue samples were homogenized in phenol, isoamyl alcohol, guanidinium isothiocyanate, and 2mercaptoethanol with 18-G needles fitted onto 1-cc syringes. Monophasic homogenates were separated into 2 layers with a 20% volume of chloroform, followed by centrifugation.…”