Socially induced morphine pseudosensitization in adolescent mice

Abstract

Given that social influences are among the strongest predictors of adolescents' drug use, this study examined the effect of social interaction on morphine-induced hyperlocomotion in both adolescent and adult mice. Three experimental groups of adolescent and adult male mice were examined (i) morphine-treated mice (twice daily, 10-40 mg/kg, subcutaneous), (ii) saline-injected mice housed together with the morphine-treated mice ('saline cage-mates'), and (iii) saline-injected mice housed physically and visually separated from the morphine-treated mice ('saline alone'). After the treatment period, mice were tested individually for their locomotor response to 10 mg/kg morphine (subcutaneous). Adolescent saline cage-mates, though administered morphine for the very first time, exhibited an enhanced hyperlocomotion response similar to the locomotor sensitization response exhibited by the morphine-treated mice. This was not observed in adults. In adults, there were no significant differences in morphine-induced hyperlocomotion between saline alone and saline cage-mates. As expected, morphine-treated adults and adolescents both exhibited locomotor sensitization. These results show a vulnerability to social influences in adolescent mice, which does not exist in adult mice.

Fig. 1. Morphine-induced hyper-locomotion in adolescent mice

Mice were injected twice daily for 6 consecutive days with saline or morphine. Locomotion was recorded 9 days following the final injection of morphine or saline (i.e. experimental day 15, Table 1). Baseline locomotion activity was recorded for 60 minutes. All mice were then injected with 10 mg/kg morphine and recorded for another 60 minutes. (A) Total distance traveled (cm) in the 60 minutes prior to morphine administration (Baseline, White bars) and in the 60 minutes post morphine administration (Morphine, Gray bars). ($) indicates a significant difference from baseline (p<0.001); (#) indicates a significant difference from saline alone mice (p<0.001) (B) Total distance traveled (cm) during the entire 120 minute test, segmented into 5 minute intervals. Arrow indicates time of morphine administration. ● - saline alone mice; □ - morphine pretreated mice; and - saline cage-mates. (*) indicates a significant difference from saline alone mice (p<0.05); (#) indicates a significant difference from saline alone mice (p<0.001). Results are presented as mean ± SEM.

Fig. 2. Morphine-induced hyper-locomotion in adult mice

Mice were injected twice daily for 6 consecutive days with saline or morphine. Locomotion was recorded 9 days following the final injection of morphine or saline (i.e. experimental day 15, Table 1). Baseline locomotion activity was recorded for 60 minutes. All mice were then injected with 10 mg/kg morphine and recorded for another 60 minutes. (A) Total distance traveled (cm) in the 60 minutes prior to morphine administration (Baseline, White bars) and in the 60 minutes post-morphine administration (Morphine, Gray bars). ($) indicates a significant difference from baseline (p<0.001); (#) indicates a significant difference from saline alone mice (p<0.001) (B) Total distance traveled (cm) during the entire 120 minute test, segmented into 5 minute intervals. Arrow indicates time of morphine administration. ● - saline alone mice; □ - morphine pretreated mice; and - saline cage-mate mice. (*) indicates a significant difference from saline alone mice (p<0.05); (#) indicates a significant difference from saline alone mice (p<0.001). Results are presented as mean ± SEM.