Activity of presumed dopamine neurons in the ventral tegmental area during heroin self-administration

To assess the pattern of mesocorticolimbic dopamine (DA) activity associated with drug-seeking and drug-taking behavior, we monitored the firing rate of presumed DA neurons in the ventral tegmental area of trained rats during i.v. heroin self-administration (SA). Relative to a slow and irregular basal activity, the first SA of each session was preceded by a phasic increase and followed by a more persistent increase in discharge rate that peaked approximately 15-20 min later at the time of the second SA. All subsequent SAs were associated with a biphasic neuronal change: a transient decrease followed by a gradual increase that peaked just before the next SA. Our results support mesocorticolimbic DA activation in heroin-seeking behavior but suggest a transient inhibition of DA activity correlated with heroin reward.