Sex differences in affective response to opioid withdrawal during adolescence

Drug withdrawal is suggested to play a role in precipitating mood disorders in individuals with familial predisposition. Age-related differences in affective responses to withdrawal might explain the increased risk of mental illnesses when drug use begins during adolescence. Recently we observed that, in contrast to adult male mice, adolescent males exhibited a decrease in immobility in the forced swim test on the third day of withdrawal, as compared with controls. Thus, the present study examined forced swim test behaviors of adolescent female mice during opioid withdrawal. Similar to the male study, adolescent female mice were injected with two morphine regimens which differed in dosage. Three and nine days following discontinuation of morphine administration, forced swim test immobility time and locomotion were evaluated. In contrast to males, which exhibited a decrease in immobility, no significant differences in immobility were observed in female adolescents undergoing withdrawal as compared with saline-injected controls. This sex difference in forced swim test behaviors was not due to changes in overall motor activity, since differences in locomotion were not observed in either male or female adolescent mice. Thus, this study demonstrates sex differences in forced swim test behavior during opioid withdrawal. Forced swim test behaviors are classically used to evaluate mood in rodents, thus this study suggests that opioid withdrawal might affect mood differentially across sexes.