Examining the impact of adolescent social isolation on oxycodone sensitization

Chronic stress and social isolation during adolescence can disrupt normal development and increase substance use behaviors in adulthood.

The impact of adolescent social isolation stress on stimulant behaviors has been identified in a mouse model. The impact of adolescent social isolation on opioid behaviors is less clear. We assess the effect of adolescent social isolation on oxycodone sensitization across sexes and light phase.

Mice were either group-housed or socially isolated at weaning and remained in these housing conditions until adulthood. Male and female mice in both housing conditions received 5 days of daily injections of oxycodone (5 mg/kg) during either the light or dark phase. A subset of mice remained in their home cage for five additional days prior to a final oxycodone challenge.

When tested during the light phase male mice in both housing conditions exhibit oxycodone sensitization to a 5 mg/kg dose, while female mice do not. In contrast, when tested during the dark phase, none of the groups exhibit oxycodone sensitization. In fact, female mice develop tolerance to the locomotor activating effects of oxycodone after five daily injections. Following five days in the home cage, group housed females continued to exhibit tolerance to the locomotor effects of oxycodone, while socially isolated females do not. Additionally, socially isolated females exhibit a larger conditioned response to the arena during the habituation phase than animals in any of the other groups.

Sensitization is a light phase dependent process in male mice. Female mice do not sensitize to 5 mg/kg oxycodone. Adolescent social isolation stress influences the development of tolerance, not sensitization. Oxycodone induces sex-specific effects on locomotion during habituation phase.