Neural response to stress differs by sex in young adulthood.

Increase in stress-related disorders in women begins post-puberty and persists throughout the lifespan. To characterize sex differences in stress response in early adulthood, we used functional magnetic resonance imaging while participants underwent a stress task in conjunction with serum cortisol levels and questionnaires assessing anxiety and mood. Forty-two healthy subjects aged 18-25 years participated (21M, 21F). Interaction of stress and sex in brain activation and connectivity were examined. Results demonstrated significant sex differences in brain activity with women exhibiting increased activation in regions that inhibit arousal compared to men during the stress paradigm. Women had increased connectivity among stress circuitry regions and default mode network, whereas men had increased connectivity between stress and cognitive control regions. In a subset of subjects (13F, 17M), we obtained gamma-aminobutyric acid (GABA) magnetic resonance spectroscopy in rostral anterior cingulate cortex (rostral ACC) and dorsolateral prefrotal cortex (dlPFC) and conducted exploratory analyses to relate GABA measurements with sex differences in brain activation and connectivity. Prefrontal GABA levels were negatively associated with inferior temporal gyrus activation in men and women and with ventromedial prefrontal cortex activation in men. Despite sex differences in neural response, we found similar subjective ratings of anxiety and mood, cortisol levels, and GABA levels between sexes, suggesting sex differences in brain activity result in similar behavioral responses among the sexes. These results help establish sex differences in healthy brain activity from which we can better understand sex differences underlying stress-associated illnesses.

Involvement of dopamine, but not norepinephrine, in the sex-specific regulation of juvenile socially rewarding behavior by vasopressin.

Social play is a highly rewarding behavior displayed mostly during the juvenile period. We recently showed that vasopressin V1a receptor (V1aR) blockade in the lateral septum (LS) enhances social play in male juvenile rats, but reduces it in females. Here, we determined whether the LS-AVP system modulates dopamine (DA) and/or norepinephrine (NE) neurotransmission in the LS to regulate social play behavior in sex-specific ways. Using microdialysis combined with retrodialysis, we demonstrated that both LS-AVP administration and social play exposure increased extracellular LS-DA release in females, but not in males. Pharmacological blockade of LS-DA receptors reduced social play in both sexes, but required a higher dose in females. This suggests that baseline LS-DA release is sufficient for social play in males, while increased LS-DA release is necessary for social play in females. Administration of a V1aR antagonist into the LS inhibited the social play-induced increase in extracellular LS-DA release in females. Furthermore, co-administration of the DA agonist apomorphine prevented the LS-V1aR blockade-induced decrease in social play in females. This suggests that LS-V1aR blockade reduces social play in females by dampening the rise in LS-DA release. Extracellular LS-NE release was enhanced in response to pharmacological manipulations of the LS-AVP system and to social play in males and/or females, but pharmacological blockade or stimulation of LS-NE receptors did not alter social play in either sex. Overall, we define a mechanism by which the LS-AVP system alters LS-DA neurotransmission differently in males than females resulting in the sex-specific regulation of juvenile social play behavior.

The Phenotypic Effects of Royal Jelly on Wild-Type D. melanogaster Are Strain-Specific.

The role for royal jelly (RJ) in promoting caste differentiation of honeybee larvae into queens rather than workers is well characterized. A recent study demonstrated that this poorly understood complex nutrition drives strikingly similar phenotypic effects in Drosophila melanogaster, such as increased body size and reduced developmental time, making possible the use of D. melanogaster as a model system for the genetic analysis of the cellular mechanisms underlying RJ and caste differentiation. We demonstrate here that RJ increases the body size of some wild-type strains of D. melanogaster but not others, and report significant delays in developmental time in all flies reared on RJ. These findings suggest that cryptic genetic variation may be a factor in the D. melanogaster response to RJ, and should be considered when attempting to elucidate response mechanisms to environmental changes in non-honeybee species.

Long-term wheel-running and acute 6-h advances alter glucose tolerance and insulin levels in TALLYHO/JngJ mice.

Studies have shown a relationship between circadian rhythm disruptions and type-2 diabetes. This investigation examined the effects of circadian disruption (6-h phase advances) on the progression of diabetes in a type-2 diabetic mouse model -TALLYHO/JngJ - and whether wheel-running can alleviate the effects of the phase advances. 6-h advances alter fasting glucose, glucose tolerance and insulin production. Wheel-running reduced body mass, improved glucose tolerance and reduced insulin in TALLYHO/JngJ and alleviated some of the changes in diabetic symptoms due to 6-h advances. These results indicate that individuals with type-2 diabetes can benefit from physical activity and exercise can be a countermeasure to offset the effects of an acute phase advance.

Alcohol and lithium have opposing effects on the period and phase of the behavioral free-running activity rhythm.

Bipolar patients have a high prevalence of comorbid alcohol use and abuse disorders, while chronic alcohol drinking may increase the presence and severity of certain symptoms of bipolar disorder. As such, there may be many individuals that are prescribed lithium to alleviate the manic symptoms of bipolar disorder, but also drink alcohol concurrently. In addition, both alcoholics and individuals with bipolar disorder often exhibit disruptions to their sleep-wake cycles and other circadian rhythms. Interestingly, both ethanol and lithium are known to alter both the period and the phase of free-running rhythms in mammals. While lithium is known to lengthen the period, ethanol seems to shorten the period and attenuate the responses to acute light pulses. Therefore, the present study aimed to determine whether ethanol and lithium have opposing effects on the circadian pacemaker when administered together. C57BL/6J mice were provided drinking solutions containing lithium, alcohol, or both, and their free-running rhythms along with their response to photic phase shifts were investigated. Mice treated with lithium displayed period lengthening, which was almost completely negated when ethanol was added. Moreover, ethanol significantly attenuated light-induced phase delays while the addition of lithium partially restored this response. These results indicate that alcohol and lithium have opposing effects on behavioral circadian rhythms. Individuals with bipolar disorder who are prescribed lithium and who drink alcohol might be inadvertently altering their sleep and circadian cycles, which may exacerbate their symptoms.