Morphine administration during low ovarian hormone stage results in transient over expression of fear memories in females

Abstract

Acute exposure to morphine after a traumatic event reduces trauma related symptoms in humans and conditioned fear expression in male rats. We aimed to determine whether acute administration of morphine alters consolidation of fear learning and extinction. Male and female rats in proestrus and metaestrus (high and low ovarian hormones respectively) underwent fear conditioning and received saline or morphine (2.5 mg/kg s.c.). The next day they underwent extinction. Results showed increased freezing during extinction only in the morphine metaestrus group while morphine did not affect males or proestrus females. Recall of extinction was similar on all groups. On a second experiment, a subset of rats conditioned during metaestrus was administered morphine prior to extinction producing no effects. We then measured mu opioid receptor (MOR) expression in the amygdala and periaqueductal gray (PAG) at the end of extinction (day 2). In males and proestrus females, morphine caused an increase in MOR in the amygdala but no in the PAG. In metaestrus females, morphine did not change MOR expression in either structure. These data suggests that ovarian hormones may interact with MORs in the amygdala to transiently alter memory consolidation. Morphine given after trauma to females with low ovarian hormones might increase the recall of fear responses, making recovery harder.

Antagonizing the corticotropin releasing hormone receptor 1 with antalarmin reduces the progression of endometriosis

“…Western blot experiments were carried out as previously described [ 37 ] using normal uterine tissue of sham rats and the normal uterus as well as endometriosis vesicles after 7 days of endometriosis induction. We loaded 50μg of protein to identify the CRHR1 using a goat polyclonal CRHR1 antibody at a concentration of 1:250 (Abcam, Cambridge, Massachusetts, AB59023).…”

Modulation of Fear Extinction by Stress, Stress Hormones and Estradiol: A Review

“…Interestingly, there are interactions between morphine and female sex-hormone levels in fear extinction (Perez-Torres et al, 2015 ): subcutaneous morphine injections immediately after fear acquisition (day 1) led to impaired extinction acquisition (day 2) when female rats were in a cycle phase of low estradiol and low progesterone (P4) level (metestrus)—as compared to females with high levels of ovarian hormones and males. Moreover, in the metestrus group, there was no increase of μ-opioid receptor expression in the amygdala.…”

“…Moreover, the morphine dose in the 48 h after trauma was one of the predictors of PTSD severity 3 months after the trauma: patients with the later diagnosis PTSD had obtained less morphine in the aftermath of the traumatic injury (Bryant et al, 2009 ). Based on the data from Perez-Torres et al ( 2015 ), estradiol levels should be taken into account and be validated for PTSD immediately after trauma exposure.…”