Abstinence from chronic methylphenidate exposure modifies cannabinoid receptor 1 levels in the brain in a dose-dependent manner
Introduction: Methylphenidate (MP) is a widely used psychostimulant prescribed for Attention Deficit
Hyperactivity Disorder, and is also used illicitly by healthy individuals. Chronic exposure to MP has been shown to affect
physiology, behavior, and neurochemistry.
Methods: The present study examined its effect on the endocannabinoid system. Adolescent rats had daily oral access to
either water (control), low dose MP (4/10 mg/kg), or high dose MP (30/60 mg/kg). After 13 weeks of exposure, half of the
rats in each group were euthanized, however the remaining rats underwent a four-week long abstinence period. Cannabinoid
receptor 1 binding (CB1) was measured with in vitro autoradiography using [3H] SR141716A.
Results: Rats who underwent a 4-week abstinence period after exposure to chronic HD MP showed increased binding
compared to rats with no abstinence period in several cortical and basal ganglia regions of the brain. In contrast to this, rats
who underwent a 4-week abstinence period after exposure to chronic LD MP showed lower binding compared to rats with
no abstinence period in mainly the basal ganglia regions and in the hindlimb region of the somatosensory cortex. Following
4 weeks of drug abstinence, rats who were previously given HD MP showed higher [
3H] SR141716A binding than rats
given LD MP in many of the cortical and basal ganglia regions examined. These results highlight biphasic effects of MP
treatment on cannabinoid receptor levels. Abstinence from HD MP seemed to increase CB1 receptor levels while abstinence
from LD MP seemed to decrease CB1 levels.
Conclusion: Given the prolific expression of cannabinoid receptors throughout the brain, many types of behaviors may be
affected as a result of MP abstinence. Further research will be needed to help identify these behavioral changes.
Journal Title: Current Pharmaceutical Design