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Initial antidepressant treatment can paradoxically worsen symptoms in depressed adolescents by undetermined mechanisms. Interestingly, antidepressants modulate GABAA receptors, which mediate paradoxical effects of other therapeutic drugs, particularly in females. Although the neuroanatomic site of action for this paradox is unknown, elevated GABAA receptor signaling in the nucleus accumbens can disrupt motivation. We assessed fluoxetine's effects on motivated behaviors in pubescent female hamsters — anhedonia in the reward investigational preference (RIP) test as well as anxiety in the anxiety-related feeding/exploration conflict (AFEC) test. We also assessed accumbal signaling by RT-PCR and electrophysiology. Fluoxetine initially worsened motivated behaviors at puberty, relative to adulthood. It also failed to improve these behaviors as pubescent hamsters transitioned into adulthood. Low accumbal mRNA levels of multiple GABAA receptor subunits and GABA-synthesizing enzyme, GAD67, assessed by RT-PCR, suggested low GABAergic tone at puberty. Nonetheless, rapid fluoxetine-induced reductions of α5GABAA receptor and BDNF mRNA levels at puberty were consistent with age-related differences in GABAergic responses to fluoxetine and disruption of the motivational state. Whole-cell patch clamping of accumbal slices also suggested low GABAergic tone by the low amplitude of miniature inhibitory postsynaptic currents (mIPSCs) at puberty. It also confirmed age-related differences in GABAergic responses to fluoxetine. Specifically, fluoxetine potentiated mIPSC amplitude and frequency at puberty, but attenuated the amplitude during adulthood. These results implicate GABAergic tone and GABAA receptor plasticity in adverse motivational responses and resistance to fluoxetine during adolescence. [ABSTRACT FROM AUTHOR]

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 antidepressant efficacy. [ABSTRACT FROM AUTHOR]

Highlights: [•] Differential display PCR revealed candidate genes for control of fertility in testis during photoperiodic modulation. [•] Multiple linear regression modeling helped identify aquaporin-11 as the best fit among the candidate genes. [•] RNA interference of Aqp11, using small interfering RNA demonstrated Aqp11 tonically induces markers of fertility. [•] The collective results provide the first molecular evidence that Aqp11 regulates fertility. [ABSTRACT FROM AUTHOR]

Abstract: Anorexia and anxiety cause significant mortality and disability with female biases and frequent comorbidity after puberty, but the scarcity of suitable animal models impedes understanding of their biological underpinnings. It is reported here that in adult or weanling Syrian hamsters, relative to social housing (SH), social separation (SS) induced anorexia characterized as hypophagia, weight loss, reduced adiposity, and hypermetabolism. Following anorexia, SS increased reluctance to feed, and thigmotaxis, in anxiogenic environments. Importantly, anorexia and anxiety were induced post-puberty with female biases. SS also reduced hypothalamic corticotrophin-releasing factor mRNA and serum corticosteroid levels assessed by RT-PCR and RIA, respectively. Consistent with the view that sex differences in adrenal suppression contributed to female biases in anorexia and anxiety by disinhibiting neuroimmune activity, SS elevated hypothalamic interleukin-6 and toll-like receptor 4 mRNA levels. Although corticosteroids were highest during SH, they were within the physiological range and associated with juvenile-like growth of white adipose, bone, and skeletal muscle. These results suggest that hamsters exhibit plasticity in bioenergetic and emotional phenotypes across puberty without an increase in stress responsiveness. Thus, social separation of hamsters provides a model of sex differences in anorexia and anxiety during adulthood and their pathogeneses during adolescence. [Copyright &y& Elsevier]

Highlights: [•] AFEC test is modified for anxious behavior in hamsters. [•] AFEC test distinguishes anxious behavior from appetitive or consummatory behavior. [•] Food deprivation elevates anxious behavior in hamsters without increasing consummatory drive. [ABSTRACT FROM AUTHOR]

Reduced skin blood flow has been reported in neuropathic pain patients as well as various peripheral neuropathic pain model animals. We have previously shown that vasodilators, which improves reduced skin blood flow, correlatively alleviate neuropathic pain in chronic constriction injury (CCI) mice, a model of neuropathic pain from peripheral nerve injury. Here, we sought to elucidate the mechanism underlying the reduced skin blood flow in CCI rats. The skin blood flow of the ipsilateral plantar arteries was significantly reduced compared to that of the contralateral ones 4 weeks after loose ligation of the sciatic nerve. The contraction induced by noradrenaline, serotonin, and U46619, a thromboxane receptor agonist, in the isolated ipsilateral plantar arteries was significantly enhanced compared to that in the contralateral ones. KB-R7943, a Na+/Ca2+ exchanger (NCX) inhibitor, shifted the concentration-response curves of noradrenaline to the left in the contralateral arteries but had no effect on the ipsilateral side. There was no significant difference in concentration-response curves of noradrenaline between the ipsilateral and contralateral arteries in the presence of KB-R7943. Amiloride, a non-specific inhibitor of Na+ channels and transporters, comparably shifted concentration-response curves of noradrenaline to the left in both the contralateral and ipsilateral arteries. One hundred nM of noradrenaline induced intracellular Ca2+ elevation in the ipsilateral arteries, which was significantly larger than that induced by 300-nM noradrenaline in the contralateral arteries. These results suggest that reduced peripheral blood flow after nerve injury is due to Na+-dependent inactivation of NCX in the ipsilateral plantar arteries. [Display omitted] [ABSTRACT FROM AUTHOR]