Elsevier

Neuroscience

Volume 99, Issue 3, 16 August 2000, Pages 433-443
Neuroscience

Neuronal and behavioral correlations in the medial prefrontal cortex and nucleus accumbens during cocaine self-administration by rats

https://doi.org/10.1016/S0306-4522(00)00218-9Get rights and content

Abstract

Up to 31 neurons per animal were simultaneously recorded from the medial prefrontal cortex and nucleus accumbens in 15 rats during i.v. cocaine self-administration sessions, using a multi-channel, single-unit recording technique. Alterations of neuronal activity (both excitatory and inhibitory) were found a few seconds before each lever press for cocaine infusion; we have called these pre-lever press neuronal activations “anticipatory responses”. A detailed video analysis revealed that these neuronal firing alterations were associated with specific portions of the behavioral sequence performed before each lever press in both recording areas. Some of the simultaneously recorded neurons displayed similar firing patterns in relation to a given behavioral episode within the behavioral sequence (turning, raising head, etc.), while others fired at different times relative to each behavioral event. Cross-correlational analyses revealed inter-regional and intra-regional correlated firing patterns between pairs of simultaneously recorded medial prefrontal cortex and nucleus accumbens neurons. This correlated firing occurred in the neurons with and without anticipatory responses, although the incidence of correlations between anticipatory neuron pairs was much higher than that between non-anticipatory neuron pairs (18.4% vs 3.6%). Many correlated neuron pairs displayed a time lag in the peak of correlational activity that indicated a temporal sequence in correlated activity. In contradiction to our hypothesis, the temporal pattern of correlation reveals that there are more cases in which nucleus accumbens neurons fired ahead of medial prefrontal cortex neurons.

The results suggest that multiple mesocorticolimbic neuronal circuits may code sequential steps during the behavioral sequence performed to obtain an infusion of cocaine. The observed correlated firing between the medial prefrontal cortex and the nucleus accumbens indicates that dynamic, coherent activity occurs within the mesocorticolimbic circuit. Because this circuit is hypothesized to drive drug-seeking behavior, we suggest that this correlated firing between the nucleus accumbens and the medial prefrontal cortex may participate in the control of cocaine self-administration. In addition, the finding that correlated activity within the nucleus accumbens more often precedes that of the medial prefrontal cortex suggests that the nucleus accumbens may play a prime role in the initiation of cocaine self-administration.

Section snippets

Animals and surgery

Fifteen young adult male Sprague–Dawley rats weighing 250–300 g were used in these experiments. Animals were singly housed under a reverse dark–light cycle (lights off from 07.00 to 19.00). Following injection of ketamine (100 mg/kg, i.m.), silastic tubing (26 mm long, 0.3 mm i.d. cannula tubing, connected to a 90-mm-long, 0.6-mm i.d. outlet tubing) was inserted under sterile conditions in the right jugular vein for subsequent i.v. drug infusion. The infusion tubing was glued to silastic implant

General responses of medial prefrontal cortex and nucleus accumbens neurons during cocaine self-administration sessions

The data included in this study are from one cocaine self-administration session for each of 15 male Sprague–Dawley rats. A total of 328 neurons (189 mPFC and 139 NAc) were recorded from 15 cocaine self-administration sessions. A maximum of 31 neurons were recorded simultaneously in the mPFC and NAc from a subject during a cocaine self-administration session.

The single units were classified into three categories according to their responses before the lever press for cocaine

Discussion

The mesocorticolimbic system, a complex of interconnected limbic structures, plays an important role in reward-seeking behaviors.28 Studies focused on separate regions of the mesocorticolimbic system have provided evidence for the involvement of many of these individual regions in reward-seeking processes. However, it is reasonable to propose that the execution of reward-seeking behaviors such as cocaine self-administration requires the activation and coordination of multiple regions across the

Conclusion

The present study revealed that multiple neuronal circuits, consisting of small subsets of neurons, exist in the mesocorticolimbic system mediating drug-seeking behavior. Different neuronal circuits code drug-seeking behaviors during the temporal sequence leading to cocaine self-administration. Correlated neuronal activity was detected in the mesocorticolimbic system, especially among the anticipatory neurons. The temporal relation in correlated firing revealed that NAc neurons more often fired

Acknowledgements

This study was supported by grants DA-2338 to D.J.W. and DA-10370 to J.-Y.C.

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