Dopamine transporter, but not tyrosine hydroxylase, may be implicated in determining individual differences in behavioral sensitization to amphetamine

Repeated administration of psychostimulants, such as amphetamine and cocaine, results in a long-lasting enhancement of behavioral responses elicited by a subsequent challenge injection of these drugs. This phenomenon has been termed behavioral sensitization. A well established model of individual differences based on the locomotor response to a novel environment has been shown to reliably predict the degree of behavioral sensitization to amphetamine. Rats that have high locomotor response in a novel environment (high responders or HR) develop greater behavioral sensitization to psychostimulants when compared to rats that show low locomotor activity in the same novel environment (low Responders or LR). Therefore, this model is ideal to study genetic factors that may underlie behavioral sensitization to psychostimulants. In this study, adult Sprague-Dawley rats were daily injected with amphetamine (1 mg/kg, i.p.) or saline for 9 days. Locomotor activity was recorded every other day. Following a one week-withdrawal a subsequent challenge of a lower dose of amphetamine (0.5 mg/kg, i.p.) was given to all rats (amphetamine pretreated and saline pretreated) and their locomotor activity was recorded. Our results show that HR rats, but not LR rats, develop behavioral sensitization to the locomotor activating effects of amphetamine. Furthermore, only HR rats pretreated with amphetamine exhibited an increase in dopamine transporter mRNA in the ventral tegmental area (VTA) and substantia nigra (SN). Tyrosine hydroxylase mRNA in the VTA and SN was upregulated in both HR and LR rats pretreated with amphetamine when compared to HR and LR rats pretreated with saline. These results demonstrate the existence of individual differences in behavioral sensitization to amphetamine and suggest that dopamine transporter, but not tyrosine hydroxylase, may be a critical factor in the development and expression of behavioral sensitization to the locomotor activating effects of amphetamine.