EVIDENCE FOR INVOLVEMENT OF VENTRAL TEGMENTAL AREA CYCLIC-AMP SYSTEMSIN BEHAVIORAL SENSITIZATION TO PSYCHOSTIMULANTS

The present study investigated the role of ventral tegmental area (VTA ) cyclic AMP (cAMP) systems in the behavioral sensitivity to psychosti mulants in male Sprague-Dawley rats. Bilateral microinjections of chol era toxin (CTX) into the VTA (50-500 ng/500 nl/side) dose-dependently sensitized animals to the locomotor stimulant effects of systemic d-am phetamine, cocaine and apomorphine, but were without effects on morphi ne-induced locomotion 24 hr after microinjection. The CTX-induced beha vioral sensitization to amphetamine was even greater 72 hr after micro injection, but was no longer present 14 days after intra-VTA CTX pretr eatment. Coadministration of the cAMP-dependent protein kinase inhibit or H8 into the VTA blocked CTX-induced sensitization to amphetamine, s uggesting that the sensitization is dependent on phosphorylation event s in the VTA mediated by cAMP-dependent protein kinase. Pretreatment w ith CTX did not enhance amphetamine-induced dopamine release in the nu cleus accumbens relative to saline controls 24 hr after microinjection . A single bilateral injection of d-amphetamine into the VTA (5 mu g/s ide) produced a significant sensitization to systemic amphetamine chal lenge 72 hr later, and this effect was also blocked by coadministratio n of H8 into the VTA. These results extend previous studies which have established the importance of the VTA in the development of behaviora l sensitization and suggest that cAMP systems may play a crucial role in this neuroadaptive process.