Impulse activity of ventral tegmental area neurons during heroin self-administration in rats.

To assess the pattern of mesocorticolimbic dopamine activity associated with drug-seeking and drug-taking behavior, we recorded impulse activity of ventral tegmental area neurons during intravenous heroin self-administration in trained rats. Although these neurons had considerable variability, two major groups-units with triphasic long-duration spikes and biphasic short-duration spikes-were identified. Relative to a slow and irregular basal activity of long-spike units, the first self-administration of each session was preceded by a phasic neuronal activation and followed by a more sustained drug-induced activation that reached a maximum at the time of the second self-injection. After each subsequent heroin self-injection, the discharge rate transiently decreased, correlating with the blockade of preceding motor activation and the appearance of freezing, but slowly and gradually increased again in parallel with searching behavior, reaching a maximum at the time of the next self-injection. Passive drug injections in either drug-naive, freely moving or drug-experienced, anesthetized rats caused much smaller, tonic increases in activity of long-spike units; these monophasic increases changed into biphasic responses with repeated injections. Although short-spike units had highly varying discharge rate and showed phasic activation during movement, during heroin self-injections they generally mimicked the activity pattern seen in long-spike units. Our results indicate that in behaving animals indirect "identification" of dopamine cells based on their distinctive electrophysiological features is more complex than in vitro and in anesthetized preparations. With respect to long-spike units, a candidate group of presumed dopamine neurons, our data agree with the view that mesocorticolimbic dopamine activation is important for the activational and/or motivational aspects of heroin-taking behavior and suggest the role of an abrupt termination of dopamine activation for drug reinforcement (reward). Although the neurochemical nature of long- and short-spike units is obviously different, similar changes in their activity may indicate that they are regulated by similar afferent inputs and that these inputs change similarly during drug-taking behavior.