Cocaine-induced locomotor activity is increased by prior handling in adolescent but not adult female rats

Abstract

Adolescence is a period of transition that is associated with increased levels of stress and a heightened propensity to initiate drug use. Neuronal development is still occurring during this transitional period, which includes the continued development of the dopamine system during the adolescent period. In the present study, the effects of pre-test handling on cocaine-induced locomotor activity were investigated among female adolescent and young adult rats upon presentation to a novel environment. On postnatal days (PND) 41-44 and 56-59 animals were handled (b.i.d.) in the colony room for 3 min. On PND 45 or PND 60, animals were removed from the colony room, weighed, and administered an acute injection of either cocaine or saline and presented to a novel environment where behavior was recorded for 30 min. Adolescent females (PND 45) that were handled prior to cocaine administration demonstrated elevated levels of cocaine-induced activity relative to their age-matched non-handled counterparts and also to their handled-adult counterparts. In contrast, among non-handled animals, young adults (PND 60) exhibited elevated drug-induced locomotion at several time points during the trial. Non-handled adolescent animals demonstrated the previously described "hyporesponsive" behavioral profile relative to their non-handled adult counterparts. The results from the present experiment indicate that adolescent animals may be more sensitive to basic laboratory manipulations such as pre-test handling, and care must be taken when utilizing adolescent animals in behavioral testing. Handling appears to be a sensitive manipulation in elucidating differences in cocaine-induced behavioral activation between ages.

Fig. 1

Total distance moved (TDM) collapsed across the entire 30-min session in PND 45 and PND 60 handled and non-handled animals. Data indicate that overall, cocaine-induced locomotor activity is significantly elevated in PND 45 handled animals treated with cocaine relative to non-handled PND 60 animals and all non-handled animals treated with cocaine when collapsed across the entire 30-min period. *Indicates significant difference from PND 60-handled and all non-handled animals (p < 0.05). Bars represent mean±SEM.

Fig. 2

Panel A: total distance moved in three-min intervals for PND 45 and PND 60 non-handled animals. Panel B: total distance moved in three-min intervals for PND 45 and PND 60 handled animals. Data indicate that adolescent (PND 45) animals that are handled prior to exposure to an inescapable novel environment and treated with cocaine exhibit a significant increase in TDM from 6 to 27 min of the trial, when compared to their young adult (PND 60) handled counterparts. Additionally, among non-handled animals, PND 60 cocaine-treated animals demonstrate elevated locomotor activity at 6, 12 and 15 min of the session relative to their adolescent counterparts. ^#Indicates significant difference of cocaine-induced locomotor activity between non-handled PND 45 and non-handled PND 60 animals (6, 12 and 15 min of trial; p <0.05). *Indicates significant difference of cocaine-induced locomotor activity between handled PND 45 animals and handled PND 60 animals (6–27 min of trial; p <0.05). Handled-adolescent animals exhibit greater cocaine-induced locomotor activity relative to their non-handled counterparts across the entire trial. Data points represent mean±SEM.