Dopamine Uptake Inhibitors but Not Dopamine Releasers Induce Greater Increases in Motor Behavior and Extracellular Dopamine in Adolescent Rats Than in Adult Male Rats

Most life-long drug addiction begins during adolescence. Im-portant structural and functional changes in brain occur during adolescence and developmental differences in forebrain dopa-mine systems could mediate a biologic vulnerability to drug addiction during adolescence. Studies investigating age dif-ferences in psychostimulant responses have yielded mixed results, possibly because of different mechanisms for in-creasing extracellular dopamine. Recent research from our laboratory suggests that adolescent dopamine systems may be most affected by selective dopamine uptake inhibitors. We investigated age-related behavioral responses to acute administration of several dopamine uptake inhibitors [meth-ylphenidate, 1-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-4-(3-phenylpropyl)piperazine (GBR12909), and nomifensine] and releasing agents [amphetamine and methylenedioxymeth-amphetamine (MDMA)] in adolescent and adult male rats. Methylphenidate and amphetamine effects on stimulated do-pamine efflux were determined using fast-scan cyclic volta-mmetry in vivo. Dopamine uptake inhibitors but not dopa-mine releasing agents induced more locomotion and/or stereotypy in adolescent relative to adult rats. MDMA effects were greater in adults at early time points after dosing. Methylphenidate but not amphetamine induced much greater dopamine efflux in periadolescent relative to adult rats. Periadolescent male rats are particularly sensitive to psychostimulants that are DAT inhibitors but are not inter-nalized and do not release dopamine. Immaturity of DAT and/or DAT associated signaling systems in adolescence specifically enhances behavioral and dopaminergic re-sponses in adolescence