Chronic, but not acute, buprenorphine leads to antidepressant‐like effects in both male and female mice

Abstract

Current antidepressant medications lack efficacy in a large fraction of patients and typically take weeks to reduce symptoms in individuals who do respond to treatment. However, the factors that govern treatment responses to various classes of antidepressants remain largely unknown. The incidence and presentation of mood and anxiety disorders are both characterized by sex differences, and sex differences in response to antidepressants have been reported for both selective serotonin reuptake inhibitors (SSRIs) and tricyclics (TCAs). As new antidepressants are developed, it will be critical to determine their efficacy in both male and female subjects to enable appropriate treatment selection. Previous research has investigated the antidepressant effects of buprenorphine, which has high affinity for mu opioid receptor (MOR), kappa opioid receptor (KOR), and some affinity for delta opioid receptor (DOR). Though previous studies have shown support for buprenorphine as an antidepressant, the effects have only been demonstrated in males. This study examined potential sex differences in the behavioral and molecular responses to acute and chronic buprenorphine administration in mice. The effects of buprenorphine were measured with the forced swim test, open field test, and light dark emergence test. In contrast to published research, acute buprenorphine showed no significant main effect of treatment in any of these behavioral tests in either sex. However, chronic treatment with buprenorphine showed a main effect of treatment in both the open field and forced swim tests, suggesting that both males and females are responsive to this drug. While gene expression analysis did show that female mice expressed higher levels of pro‐opiomelanocortin (POMC) in the striatum compared to males, no sex by drug interactions were observed. These studies show that chronic, but not acute, buprenorphine treatment has antidepressant effects, and that females do not appear to have reduced sensitivity to these effects.