Self‐Stimulation of the Ventral Tegmental Area Enhances Dopamine Release in the Nucleus Accumbens: A Microdialysis Study a

Several groups'-' maintain that substances of abuse such as cocaine achieve their rewarding properties by the activation of a specific reward system in the brain that also will support intracranial self-stimulation (ICSS). There are a number of advantages in the use of the ICSS procedure to study the rewarding effects of drugs, including its methodological simplicity and the high concordance between the pharmacological ticilitation of ICSS and human addiction liability data.' Most researchers who study the effects of drugs on ICSS are well aware of the possible confounds that can arise from unconditioned motor effects of the drugs and from htigue. Accordingly, procedures have been developed to measure current thresholds required to maintain ICSS. Employing this procedure, Esposito et al. showed that cocaine lowered the threshold for rewarding brain-stimulation, thereby extending Crow's6 initial report of an increase in ICSS rate by cocaine. A distinct advantage of using the ICSS procedure to study drug-reward is the information provided about neuronal circuits that may subserve the rewarding properties of drugs of abuse. A large body of data derived from pharmacological, neurotoxic lesion and postmortem neurochemical studies support the role of mesotelencephalic dopaminergic neurons in ICSS at sites in the ventral tegmental area (VTA) and parts ofthe medial foreblain bundle (MFB) (cf. refs. 2,4,7). Until recently however, critical in pivo evidence in support of this hypothesis was lacking. Two new techniques for mea-