Extrahypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance.

Oxytocin increases the salience of both positive and negative social contexts and it is thought that these diverse actions on behavior are mediated in part through circuit-specific action. This hypothesis is based primarily on manipulations of oxytocin receptor function, leaving open the question of whether different populations of oxytocin neurons mediate different effects on behavior. Here we inhibited oxytocin synthesis in a stress-sensitive population of oxytocin neurons specifically within the medioventral bed nucleus of the stria terminalis (BNSTmv). Oxytocin knockdown prevented social stress-induced increases in social vigilance and decreases in social approach. Viral tracing of BNSTmv oxytocin neurons revealed fibers in regions controlling defensive behaviors, including lateral hypothalamus, anterior hypothalamus, and anteromedial BNST (BNSTam). Oxytocin infusion into BNSTam in stress naïve mice increased social vigilance and reduced social approach. These results show that a population of extrahypothalamic oxytocin neurons plays a key role in controlling stress-induced social anxiety behaviors.

Adherence with multiple-combination antihypertensive pharmacotherapies in a US managed care database.

OBJECTIVE: The aim of this analysis was to assess the impact of multiple combination therapies on medication possession ratios (MPRs) in an antihypertensive naive population. METHODS: Data were collected using the Integrated Healthcare Information Solution's National Benchmark Database (January 1997 to June 2004). Data from patients who received 2-pill pharmacotherapy with valsartan or valsartan/hydrochlorothiazide (HCTZ) in a fixed-dose combination (FDC) + amlodipine were compared with those from patients who received 3-pill therapy with valsartan + HCTZ + amlodipine as 3 free-drug components. MPR was calculated by dividing the total days' supply for the lower value in the case of individual drug components, or the number of days' supply in the case of FDC, by 365 (the number of days during the 1-year study period the medication regimen was prescribed). A general linear regression was then performed to determine the effect of treatment group on MPR, controlling for the demographic and clinical characteristics. RESULTS: Data from 908 patients were included (527 women, 381 men; mean age, 53.9 years; 2-pill treatment with valsartan + amlodipine, 224 patients; 2-pill treatment with valsartan/HCTZ + amlodipine, 619; and 3-pill therapy with valsartan + HCTZ + amlodipine, 65). The MPR values were 75.4%, 73.1%, and 60.5%, respectively (P = 0.005). MPR improved with age (69.6% in the subset aged 18-<36 years vs 75.2% in the subset aged >or=64 years; P = 0.023). CONCLUSIONS: In these antihypertensive-naive patients with hypertension, MPR decreased with the increase in tablets per regimen, and improved MPR was correlated with increasing age. These findings suggest patient compliance improves with simplified pharmacotherapeutic approaches.