Estradiol reduction through aromatase inhibition impairs cocaine seeking in male rats.

Introduction: Clinical and preclinical research on cocaine use disorder (CUD) has shown that sex differences in drug seeking are influenced by hormonal fluctuations. Estradiol (E2), a sex steroid hormone, has been linked to female drug effects, vulnerability to use/abuse, and psychosocial factors. Preclinical studies show that estradiol in females facilitates the extinction of cocaine-seeking behavior indicating a possible role in regulating extinction learning. Similar to females, males' brains contain the aromatase enzyme which converts testosterone to estradiol. However, it is unclear whether estradiol plays a role in male extinction learning as it does in females. Furthermore, how endogenously aromatized estradiol affects drug addiction in males is unknown. Therefore, this study investigated whether endogenous estradiol regulates cocaine seeking in male rats. We hypothesized that decreased aromatase enzyme activity, resulting in decreased estradiol synthesis in male brains, will impair extinction learning leading to increased cocaine-seeking behavior. Methods: This hypothesis was tested using cocaine-conditioned place preference (CPP), and short access self-administration (SA), followed by extinction and reinstatement. Before each extinction session for CPP or SA, male rats received an injection of either 1 (low dose) or 2.5 mg/kg (high dose) of the aromatase inhibitor Fadrozole (FAD), or vehicle. Results: FAD groups showed dose-dependent effects on cocaine-seeking behavior compared to the vehicle group during CPP extinction. Specifically, low dose FAD facilitated extinction of cocaine CPP, whereas high dose FAD impaired it. In contrast, neither dose of FAD had any effects on the extinction of cocaine SA. Interestingly, only the low dose FAD group had decreased active lever pressing during cue- and cocaine-primed reinstatement compared to the vehicle group. Neither dose of FAD had an effect on sucrose extinction or reinstatement of sucrose seeking. Discussion: These results from CPP experiments suggest that estradiol may impact extinction learning, as a low dose of FAD may strengthen the formation of cocaine extinction memory. Additionally, in male rats undergoing cocaine SA, the same low dose of aromatase inhibitor effectively reduced reinstatement of cocaine-seeking behavior. Thus, estradiol impacts cocaine seeking and extinction in both males and females, and it may also influence the development of sex-specific treatment strategies for CUD.

Aerobic exercise as a promising nonpharmacological therapy for the treatment of substance use disorders.

Despite the prevalence and public health impact of substance use disorders (SUDs), effective long-term treatments remain elusive. Aerobic exercise is a promising, nonpharmacological treatment currently under investigation as a strategy for preventing drug relapse. Aerobic exercise could be incorporated into the comprehensive treatment regimens for people with substance abuse disorders. Preclinical studies of SUD with animal models have shown that aerobic exercise diminishes drug-seeking behavior, which leads to relapse, in both male and female rats. Nevertheless, little is known regarding the effects of substance abuse-induced cellular and physiological adaptations believed to be responsible for drug-seeking behavior. Accordingly, the overall goal of this review is to provide a summary and an assessment of findings to date, highlighting evidence of the molecular and neurological effects of exercise on adaptations associated with SUD.

Ovarian hormones modify anxiety behavior and glucocorticoid receptors after chronic social isolation stress.

Chronic social isolation could lead to a disruption in the Hypothalamic-Pituitary-Adrenal (HPA) axis, resulting in anxiety and depressive-like behaviors but cycling estrogens could modify these behaviors. The aim of this study was to determine if changes in ovarian hormones during the normal cycle could interact with social isolation to alter anxiety and depressive-like behaviors. In parallel, we examined the expression of glucocorticoid receptor (GR) and synaptic vesicle protein synaptophysin in the hippocampus and hypothalamus of Sprague Dawley normal cycling female rats. We assigned rats to either isolated or paired housing for 8 weeks. To assess anxiety and depressive-like behaviors, we used the open field test and forced swim test, respectively. Female rats were tested at either diestrus, estrus, or proestrus stage of the estrous cycle. After behaviors, rats were perfused and brains collected. Brain sections containing hippocampus and hypothalamus were analyzed using immunohistochemistry for synaptophysin and glucocorticoid receptor (GR) levels. We found an increase in depressive-like behaviors for isolated animals compared to paired housed rats, regardless of the estrous cycle stage. Interestingly, we found a decrease in anxiety behaviors in females in the estrus stage accompanied by a decrease in GR expression in hippocampal DG and CA3. However, no changes in synaptophysin were observed in any of the areas of studied. Our results support the beneficial effects of circulating ovarian hormones in anxiety, possibly by decreasing GR expression.

Life Science's Average Publishable Unit (APU) Has Increased over the Past Two Decades.

Quantitative analysis of the scientific literature is important for evaluating the evolution and state of science. To study how the density of biological literature has changed over the past two decades we visually inspected 1464 research articles related only to the biological sciences from ten scholarly journals (with average Impact Factors, IF, ranging from 3.8 to 32.1). By scoring the number of data items (tables and figures), density of composite figures (labeled panels per figure or PPF), as well as the number of authors, pages and references per research publication we calculated an Average Publishable Unit or APU for 1993, 2003, and 2013. The data show an overall increase in the average ± SD number of data items from 1993 to 2013 of approximately 7±3 to 14±11 and PPF ratio of 2±1 to 4±2 per article, suggesting that the APU has doubled in size over the past two decades. As expected, the increase in data items per article is mainly in the form of supplemental material, constituting 0 to 80% of the data items per publication in 2013, depending on the journal. The changes in the average number of pages (approx. 8±3 to 10±3), references (approx. 44±18 to 56±24) and authors (approx. 5±3 to 8±9) per article are also presented and discussed. The average number of data items, figure density and authors per publication are correlated with the journal's average IF. The increasing APU size over time is important when considering the value of research articles for life scientists and publishers, as well as, the implications of these increasing trends in the mechanisms and economics of scientific communication.