Interaction of environment and chronic methylphenidate on anxiety‐like behavior and dopamine receptors in adolescent rodents

Abstract

Environmental rearing conditions are reported to alter behavior and dopamine (DA) transmission in rodents. Administration of DA‐ergic drugs, such as methylphenidate (MPH), may have varying effects depending on environmental exposure. This study explored the interactive effects of environment and chronic MPH on DA receptors and anxiety‐like behavior in adolescent rats. Sprague‐ Dawley rats (PND 21; n=8/group) were housed in isolated/impoverished (II), pair‐housed (PH), or socially/environmentally enriched (EE) conditions for 4 weeks. At 1 week, rats were implanted with ALZET minipumps that delivered saline or MPH (2 or 8 mg/kg/day) for 3 weeks. Post treatment, rats were tested for locomotor behavior and anxiety‐like behavior in an elevated plus maze (EPM). Rats were sacrificed at PND 50; brains processed for in vitro autoradiography to quantify DA D1 and D2 receptors in striatal regions. II rats had greater locomotor activity and spent less time in the open arms of the EPM than EE and PH rats. Environment did not affect the density of D1 or D2 receptors in striatal regions. MPH did not impact any measure of behavior. However, there was a dose‐dependent decrease in DA D2 receptor density in caudate putamen and a similar trend in accumbens across housing groups. While D1 receptor density was not affected by MPH across housing groups, preliminary results suggest that D1 receptors were increased by 8 mg/kg/day MPH in II rats, but decreased in PH and EE animals. Differences in locomotor and anxiety‐like behavior between II, PH, and EE animals highlight the importance of considering housing conditions in rodent studies. MPH did not impact behavior, but did decrease D2 receptor density across housing conditions. Despite no main effect of MPH on D1 receptors, there was a trend towards an interaction between MPH and housing. Thus, chronic MPH causes alterations in DA systems, which may appear more pronounced in animals with a history of isolation.