Dr. Dinah Ramos

Universidad Pontificia Católica de Puerto Rico

dinah_ramos@pucpr.edu

“Characterization of the behavioral and molecular profile of male and female rats during protracted morphine withdrawal”

Project Summary

Chronic exposure to morphine can lead to the development of physical dependence, at which point the

individual feels a need for continuing use of the drug just to avoid the aversive symptoms of withdrawal.

However, even if these symptoms disappear, the individual undergoes a protracted withdrawal phase that

can lead to the development of affective disorders. We have previously found that male rats undergoing

protracted morphine withdrawal show impairments in fear extinction. Female rats, however, do not show

these impairments, demonstrating sex differences in the behavioral profiles of animals undergoing protracted withdrawal. Upon examination of the brains of these animals, an increase in the expression of estrogen receptors was observed in morphine treated females but not males. This suggests a neuroprotective role of estrogen against the effects of morphine in females. Other studies from our collaborator showed that female hormones regulate conditioned place aversion induced by morphine withdrawal, further supporting a role for these hormones in the mechanisms underlying sex differences during morphine withdrawal. It is, therefore, possible that sex hormones are regulating cellular events in the brain that underlie the different behavioral profiles observed in animals undergoing protracted withdrawal. This could, in turn, play a role in the differential risks of morphine dependent males and females to develop affective disorders. Given the attributed neuroprotective role of estrogen and our preliminary data showing increases in its receptor in the brains of females and not males, it is possible that it underlies sex differences in the behavioral responses to morphine. We are, therefore, interested in identifying proteins that interact with estrogen receptors that could potentially alter their activity. We are also interested in the associated signaling cascades that may promote the different behavioral profiles observed in male and female rats undergoing protracted morphine withdrawal. Results from this study will provide an insight into the intracellular events underlying the behavioral effects of morphine dependence and protracted withdrawal that could increase the risk for developing affective disorders.