Sex differences have been identified in many of the behavioral and physiological effects of cannabinoids. While estrogens has been linked to some of these variations, the effects of estrogen on cannabinoid receptor binding have not been characterized within regions of the brain specifically implicated in stress responsivity and emotional behavior. To examine sex differences, and the role of estradiol, in regulation of the cannabinoid receptor, we compared the binding site density of the cannabinoid receptor within the amygdala, hippocampus and hypothalamus in males, cycling females, ovariectomized (OVX) females and estradiol-treated OVX females (OVX + E). Our data reveal that males and OVX females have higher amounts of hypothalamic and lower amounts of amygdalar cannabinoid receptor binding relative to both cycling females and OVX + E females. Within the hippocampus, ovariectomy resulted in an upregulation of cannabinoid receptor binding. These data provide a putative biochemical mechanism mediating the observed behavioral and physiological sex differences in the effects of cannabinoids, particularly with respect to stress and emotional behavior.
Endogenous cannabinoids play an important role in the physiology and behavioral expression of stress responses. Activation of the hypothalamic-pituitary-adrenal (HPA) axis, including the release of glucocorticoids, is the fundamental hormonal response to stress. Endocannabinoid (eCB) signaling serves to maintain HPA-axis homeostasis, by buffering basal activity as well as by mediating glucocorticoid fast feedback mechanisms. Following chronic stressor exposure, eCBs are also involved in physiological and behavioral habituation processes. Behavioral consequences of stress include fear and stress-induced anxiety as well as memory formation in the context of stress, involving contextual fear conditioning and inhibitory avoidance learning. Chronic stress can also lead to depression-like symptoms. Prominent in these behavioral stress responses is the interaction between eCBs and the HPA-axis. Future directions may differentiate among eCB signaling within various brain structures/neuronal subpopulations as well as between the distinct roles of the endogenous cannabinoid ligands. Investigation into the role of the eCB system in allostatic states and recovery processes may give insight into possible therapeutic manipulations of the system in treating chronic stress-related conditions in humans.
This interdisciplinary paper hypothesizes that Rembrandt developed new painterly techniquesnovel to the early modern period -in order to engage and direct the gaze of the observer. Though these methods were not based on scientific evidence at the time, we show that they nonetheless are consistent with a contemporary understanding of human vision. Here we propose that artists in the late 'early modern' period developed the technique of textural agencyinvolving selective variation in image detail -to guide the observer's eye and thereby influence the viewing experience. The paper begins by establishing the well-known use of textural agency among modern portrait artists, before considering the possibility that Rembrandt developed these techniques in his late portraits in reaction to his Italian contemporaries. A final section brings the argument full circle, with the presentation of laboratory evidence that Rembrandt's techniques indeed guide the modern viewer's eye in the way we propose.
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