Chronic methylphenidate alters locomotor activity and dopamine transporters differently from cocaine

Continuous infusion of cocaine produces partial behavioral tolerance to its locomotor activating effects, while daily injections produce sensitization . Methylphenidate binds with a similar affinity to cocaine at the dopamine transporter, but has a much lower affinity for the serotonin transporter th an does cocaine. This study was done to compare the effects of chronic meth ylphenidate with chronic cocaine. The pattern of locomotor activity over a 7 day treatment period was significantly different from cocaine. Methylphen idate elevated activity on each day, compared to saline, yet neither tolera nce to a continuous infusion of the drug, nor sensitization to repeated dai ly injections was produced. We have previously shown that neither of these treatments with cocaine produces significant alterations in dopamine transp orter density 1 day after the end of treatment. In contrast, methylphenidat e injections significantly decreased dopamine transporters in rostral cauda te putamen, with no change in nucleus accumbens. Continuous infusion of met hylphenidate had no effect on dopamine transporters in either brain region. These findings provide further evidence that different classes of dopamine uptake inhibitors may interact with the dopamine transporter in qualitativ ely different manners. Furthermore, it is possible that the inhibition of s erotonin uptake by cocaine may contribute to the adaptations in behavioral activity that are seen during chronic treatment. (C) 1999 Elsevier Science B.V. All rights reserved.