These authors contributed equally to this work.
Deficits in dopamine clearance and locomotion in hypoinsulinemic rats unmask novel modulation of dopamine transporters by amphetamine
Article first published online: 30 JUN 2005
Journal of Neurochemistry
Volume 94, Issue 5, pages 1402–1410, September 2005
How to Cite
Owens, W. A., Sevak, R. J., Galici, R., Chang, X., Javors, M. A., Galli, A., France, C. P. and Daws, L. C. (2005), Deficits in dopamine clearance and locomotion in hypoinsulinemic rats unmask novel modulation of dopamine transporters by amphetamine. Journal of Neurochemistry, 94: 1402–1410. doi: 10.1111/j.1471-4159.2005.03289.x
- Issue published online: 30 JUN 2005
- Article first published online: 30 JUN 2005
- Received March 3, 2005; revised manuscript received May 5, 2005; accepted May 6, 2005.
- dopamine transporter;
- locomotor activity;
Insulin affects brain reward pathways and there is converging evidence that this occurs through insulin regulation of the dopamine (DA) transporter (DAT). In rats made hypoinsulinemic by fasting, synaptosomal DA uptake is reduced. Interestingly, [3H]DA uptake is increased in hypoinsulinemic rats with a history of amphetamine self-administration. The possibility that amphetamine and insulin act in concert to regulate DAT activity prompted this study. Here we show that [3H]DA uptake, measured in vitro and clearance of exogenously applied DA in vivo, is significantly reduced in rats made hypoinsulinemic by a single injection of streptozotocin. Strikingly, amphetamine (1.78 mg/kg, given every other day for 8 days) restored DA clearance in streptozotocin-treated rats but was without effect on DA clearance in saline-treated rats. Basal locomotor activity of streptozotocin-treated rats was lower compared to control rats; however, in streptozotocin-treated rats, hyperlocomotion induced by amphetamine increased over successive amphetamine injections. In saline-treated rats the locomotor stimulant effect of amphetamine remained stable across the four amphetamine injections. These results provide exciting new evidence that actions of amphetamine on DA neurotransmission are insulin-dependent and further suggest that exposure to amphetamine may cause long-lasting changes in DAT function.