Amphetamine injection into the ventral mesencephalon sensitizes rats to peripheral amphetamine and cocaine

The daily administration of indirect dopamine agonists, including amphetamine and cocaine, results in a progressive increase in the behavioral stimulant effect of these drugs. Behavioral augmentation also has been shown with opioids such as morphine, and it is known that a stimulant action on dopaminergic perikarya in the ventromedial mesencephalon is critical to the development of behavioral sensitization to morphine. To determine if amphetamine-induced behavioral sensitization might also involve the mesencephalic dopamine neurons, amphetamine was microinjected daily for 2 days into regions of the rat brain containing dopamine cell bodies (A10 and A9 dopamine regions), or dopamine terminals (nucleus accumbens and striatum), and 6 days later amphetamine was given peripherally. It was found that daily amphetamine injection into the A10 or A9 dopamine region, but not into the dopamine terminal fields, significantly potentiated the motor stimulant effect of peripherally administered amphetamine. The behavioral sensitization produced by intracranial injection of amphetamine was found to be dose-dependent. Intra-A10 injection of amphetamine also was found to potentiate the motor stimulant effect of peripheral cocaine. These data indicate that an action by amphetamine in the A10 and A9 dopamine regions may play a critical role in the development of behavioral sensitization.