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Background: The phytocannabinoid cannabidiol (CBD) exhibits anxiolytic activity and has been promoted as a potential treatment for post-traumatic stress disorders. How does CBD interact with the brain to alter behavior? We hypothesized that CBD would produce a dose-dependent reduction in brain activity and functional coupling in neural circuitry associated with fear and defense., Methods: During the scanning session awake mice were given vehicle or CBD (3, 10, or 30 mg/kg I.P.) and imaged for 10 min post treatment. Mice were also treated with the 10 mg/kg dose of CBD and imaged 1 h later for resting state BOLD functional connectivity (rsFC). Imaging data were registered to a 3D MRI mouse atlas providing site-specific information on 138 different brain areas. Blood samples were collected for CBD measurements., Results: CBD produced a dose-dependent polarization of activation along the rostral-caudal axis of the brain. The olfactory bulb and prefrontal cortex showed an increase in positive BOLD whereas the brainstem and cerebellum showed a decrease in BOLD signal. This negative BOLD affected many areas connected to the ascending reticular activating system (ARAS). The ARAS was decoupled to much of the brain but was hyperconnected to the olfactory system and prefrontal cortex., Conclusion: The CBD-induced decrease in ARAS activity is consistent with an emerging literature suggesting that CBD reduces autonomic arousal under conditions of emotional and physical stress.

Objective: In this study, empathy is quantified using a novel social test. Empathy and prosocial behavior are linked to the expression of oxytocin in humans and rodent models. Specifically, prosocial behavior in prairie voles (Microtus ochrogaster) has been linked to the expression of oxytocin in the paraventricular nucleus of the hypothalamus. The animal's behavior was considered empathic if it spends significantly more time attempting to remove a loos fitting restraint (tether) from the stimulus animal than time in contact with a, simultaneously presented, non-social object similar to the tether. The behavioral data was cross-referenced with the number of neurons expressing oxytocin and arginine vasopressin, as well as the density of dopaminergic neurons (identified by the expression of tyrosine hydroxylase), in the paraventricular nucleus of the hypothalamus. These proteins influence empathic behavior in humans, non-human primates, rats, mice, and prairie voles., Results: The consistency between neuroanatomical mechanisms linked to empathy, and the durations of time spent engaging in empathic contact, support the prediction that the empathic contact in this test is a distinct prosocial behavior, lacking prior behavioral training or the naturally occurring ethological relevance of other prosocial behaviors, and is a measure of empathy.

Background: Previous studies have demonstrated that neonatal manipulation of oxytocin (OT) has effects on the expression of estrogen receptor alpha (ER alpha) and the central production of oxytocin observed in juveniles (at weaning, 21 days of age). The goal of this study was to determine whether the effects of neonatal manipulation of OT last into adulthood, and if the effects differ from those observed during the early postnatal period. On the first day of life, prairie voles (Microtus ochrogaster) received one of three doses of OT (High, 3 microg; Med, 0.3 microg; Low, 0.03 microg), an OT antagonist, or isotonic saline. Another group was handled, but not injected. Then as adults, brains were collected, sectioned, and stained for ER alpha or OT using immunocytochemistry., Results: In females, treatment with OT increased the expression of ER alpha immunoreactivity in the ventral lateral septum (0.03 microg) and the ventromedial nucleus of the hypothalamus and central amygdala (0.3 microg). In males, OT antagonist increased ER alpha expression in the bed nucleus of the stria terminalis. There was no apparent effect of OT on the number of cells producing OT in the paraventricular nucleus of the hypothalamus., Conclusion: The current results suggest that neonatal manipulation of OT has long-term organizational effects on the expression of ER alpha in both males and females. The lack of effect on OT neurons in the paraventricular nucleus suggests that some developmental effects of OT previously observed in weanlings do not persist into adulthood. Developmental effects of OT on ER alpha patterns were sexually dimorphic, dose-dependent, and site-specific.