Decreases in behavioral and striatal neuronal responses to dexamphetamine with aging.

Striatal neurons of mature rats responded to 2.5 mg/kg dexamphetamine with increased multiple unit activity that followed the time course of drug-increased behavior. In contrast, in older (middle-aged) rats striatal neurons failed to respond to dexamphetamine with excitation. Behavioral responses were reduced by half as compared to mature rats. Retesting of these middle-aged rats with dexamphetamine did not result in either improved behavioral or neuronal responses and decreases in spontaneous MUA suggested dexamphetamine neurotoxicity in older animals. Since striatal neuronal responses and behavioral responses to dexamphetamine are greatly reduced, age-related impairment of dopaminergic neurotransmission may lead to in reductions in striatal neuronal excitation as well as feedback from dexamphetamine-induced behavior.