Repeated administration of methylphenidate in young, adolescent, and mature rats affects the response to cocaine later in adulthood

Rationale: Previous studies have shown that the expression of behavioral sensitization to psychostimulants depends on the age and gender of the animal. Objective: This study was conducted to determine the pattern of behavioral sensitization to repeated administration of methylphenidate (MPD) at three different developmental ages and to assess the response to a cocaine challenge in adulthood. Methods: We gave five daily i.p. injections of 10 or 20 mg kg(-1) of MPD (10 MPD, 20 MPD) or saline to male and female rats beginning on postnatal days (PND) 21, 45, or 60. When all groups reached PND 90, rats were challenged with 10 mg kg(-1) cocaine. For both MPD administration and cocaine challenge, locomotion and stereotyped behaviors were assessed for 1 h. Results: The 10 MPD dose produced increased locomotion over the other two treatments at all ages. Rats that received 20 MPD showed a decline in locomotion across days with an increase in the time spent in high intensity stereotypy by day 5. Animals treated with 10 MPD showed diverse behavioral responses with adolescents showing somewhat dampened stereotypy than the other two age groups. In response to cocaine, pretreatment with MPD at all ages enhanced the cocaine response and produced qualitatively different patterns of stereotyped behavior for each gender and pretreatment age group. Conclusion: MPD produced clear age-specific sensitization of behavior in rats. Furthermore, exposure to MPD cross-sensitized with cocaine regardless of the age at which MPD exposure occurred with each pretreatment age group showing a unique pattern of responses.