Sensitization to repeated enkephalin administration into the ventral tegmental area of the rat. II. Involvement of the mesolimbic dopamine system.

In the preceding report it was shown that daily microinjection with the enkephalin analog, D-Ala2-Met5-enkephalinamide (DALA), into the ventral tegmental area (VTA) results in a progressive increase in spontaneous motor activity. In this study it was found that the enhanced behavioral response was associated with a greater increase in dopamine metabolism in the nucleus accumbens and striatum after acute DALA administration. However, daily injection with either DALA or saline did not alter the steady-state levels of dopamine or its metabolites. Haloperidol did not block the development of an augmented behavioral response. Rats pretreated with daily intra-VTA injections of DALA had a significantly greater motor response to amphetamine, i.p. or neurotensin, intra-VTA, when compared with rats pretreated with daily saline. However, the motor effects of caffeine or intraaccumbens injection with dopamine were not altered by daily injections. These data support the idea that daily intra-VTA injection with DALA results in an increased responsiveness of mesolimbic dopamine neurons to excitatory pharmacological stimuli.