Neuronal spike activity in rat nucleus accumbens during cocaine self-administration under different fixed-ratio schedules.

Chronic ensemble recording techniques were used to investigate neuronal activity in the nucleus accumbens in freely moving rats during different cocaine self-administration schedules. The issue of concern in this study was the role of nucleus accumbens in initiating and sustaining cocaine self-administration. Specifically, to determine the nature of the neuronal activity, either motor or motivational, which precedes the multiple bar presses required to self-administer cocaine and of the post-lever press neuronal response, we used conventional fixed ratio-5, fixed ratio-10, and modified fixed ratio-3 schedules. In the modified fixed ratio-3 schedule, the first lever press resulted in retraction of the lever for 2 s; the second lever press retracted the lever and turned on a cue light; the third lever press turned off the cue light and delivered cocaine (1.0 mg/kg) intravenously. In the fixed ratio-5 and -10 schedules, rats continuously pressed the lever 5 or 10 times, respectively, to obtain a single infusion of cocaine. Phasic alterations in neural spike activity were observed in 50% of nucleus accumbens neurons before (termed "anticipatory" responses) and after lever pressing for cocaine self-administration. Neurons with anticipatory responses typically exhibited such responses for all lever presses in the modified fixed ratio-3, fixed ratio-5, and fixed ratio-10 schedules, but instances were found when the activity correlate was absent. In addition, some neurons had a prominent alteration in firing rate lasting 1-5 min after cocaine self-administration, and some of these neurons also had anticipatory responses. When cocaine was eliminated during self-administration sessions, the post-lever press inhibitory responses were largely abolished or even reversed, whereas anticipatory responses were not markedly changed when rapid lever presses occurred before behavior ceased. Post-cocaine inhibitory responses compared between self-administered and passively administered cocaine were not significantly different between these two conditions. The results suggest that nucleus accumbens may be involved in initiating general reward-seeking behaviors and action which are not exclusively associated with cocaine self-administration. Moreover, the neuronal responses in the nucleus accumbens to cocaine self-administration may play an essential role in maintaining cocaine reinforcement.