Past research with the spontaneously hypertensive rat (SHR) model of
attention deficit/hyperactivity disorder showed that adolescent
methylphenidate treatment enhanced
cocaine abuse risk in SHR during adulthood. The acquisition of
cocaine self-administration was faster, and
cocaine dose-response functions were shifted upward under fixed-ratio and progressive ratio schedules compared to adult SHR that received adolescent vehicle treatment or to control strains that received adolescent
methylphenidate treatment. The current study determined if extending treatment beyond adolescence would ameliorate long-term consequences of adolescent
methylphenidate treatment on
cocaine abuse risk in adult SHR. Treatments (vehicle or 1.5mg/kg/day oral
methylphenidate) began on postnatal day 28. Groups of male SHR were treated with vehicle during adolescence and adulthood, with
methylphenidate during adolescence and vehicle during adulthood, or with
methylphenidate during adolescence and adulthood. The group receiving adolescent-only
methylphenidate was switched to vehicle on P56.
Cocaine self-administration began on postnatal day 77, and groups receiving
methylphenidate during adolescence and adulthood were treated either 1-h before or 1-h after daily sessions. At baseline under a fixed-ratio 1 schedule,
cocaine self-administration (2h sessions; 0.3mg/kg unit dose) did not differ among the four treatment groups. Under a progressive ratio schedule (4.5h maximum session length; 0.01-1.0mg/kg unit doses), breakpoints for self-administered
cocaine in SHR receiving the adult
methylphenidate treatment 1-h pre-session were not different from the vehicle control group. However, compared to the vehicle control group, breakpoints for self-administered
cocaine at the 0.3 and 1.0mg/kg unit doses were greater in adult SHR that received adolescent-only
methylphenidate or received
methylphenidate that was continued into adulthood and administered 1-h post-session. These findings suggest that extending
methylphenidate treatment beyond adolescence does not ameliorate explicitly the long-term consequences of adolescent
methylphenidate treatment. Pre-session
methylphenidate may mask temporarily the detection of an increase in
cocaine self-administration following chronic
methylphenidate treatment.