Elsevier

Neuroscience

Volume 113, Issue 4, 10 September 2002, Pages 749-753
Neuroscience

Letter to Neuroscience
Repeated cocaine administration alters the electrophysiological properties of prefrontal cortical neurons

https://doi.org/10.1016/S0306-4522(02)00246-4Get rights and content

Abstract

Recently it has become clear that some of the symptoms of addiction such as relapse to drug-taking behavior arise, in part, from a dysfunction in cognitive and emotional processing. This realization has promoted investigations into the physiology and pathophysiology of forebrain circuits that are both innervated by dopamine and play an important role in cognitive processing, including the prefrontal cortex. In order to study long-term neuroadaptations occurring in the prefrontal cortex of the rat as a consequence of psychostimulant administration, cocaine was repeatedly administered in either a contingent or a non-contingent manner. At least 2 weeks following the last cocaine injection, in vivo intracellular recordings were made from neurons located in the deep layers of the prefrontal cortex. Repeated cocaine administration abolished the presence of membrane bistability normally present in neurons located in the limbic prefrontal cortex.

These results indicate that repeated exposure to cocaine produces enduring changes in the basal activity of neurons in the prefrontal cortex that may contribute to previously identify cognitive and emotional dysfunctions in cocaine addicts.

Section snippets

Animal preparation

All the animals were handled in accordance with the procedures outlined in the Guide for the Care and Use of Laboratory Animals published by the USPHS, and the Medical University of South Carolina Animal Care and Use Committees approved the specific protocol. Subjects were male Sprague–Dawley rats (Harlan), weighing 200–250 g at the start of the experiment. Animals were housed in pairs in a temperature-controlled colony room on a 12-h light/dark cycle (lights on at 07.00 h), and food and water

Results

A total of 32 cells in 25 rats were recorded in the deep layers of the PFC (prelimbic and infralimbic cortex). In 14 control animals, 15 cells were recorded, and 17 neurons were recorded in 11 animals pretreated with cocaine. Given that there were no statistically significant differences between contingent and non-contingent groups, the results were pooled together.

Using electrical stimulation of cortical afferents, 60% of the cortical cells recorded were identified as cortico-thalamic neurons

Discussion

The most striking finding from the present report is the lack of membrane bistability in PFC neurons in rats withdrawn from repeated cocaine treatment. Consistent with previous reports using in vivo intracellular recordings in the PFC (Steriade et al., 1993, Lewis and O’Donnell, 2000), nearly 50% of pyramidal cells recorded from control animals exhibited bistability. The depolarized phase or Up state of the membrane polarization has a long duration (up to 800 ms) and the shift to the Up state

Conclusion

The present data indicate that long-term neuroadaptations are produced in PFC pyramidal cells by repeated cocaine treatment. The abolition of membrane bistability following repeated cocaine administration is consistent with reported hypofrontality in psychostimulant addicts (Jentsch and Taylor, 1999, Rogers et al., 1999, Ornstein et al., 2000, Grant et al., 2000). Thus, it appears that up to 3 weeks after withdrawal from repeated cocaine, synchrony and/or integration of glutamatergic inputs to

Acknowledgements

The authors thank Dr. J. Cornish for assistance in the cocaine self-administration paradigms. In addition, we gratefully acknowledge Dr. David Jentsch, Dr. Holly Moore and Dr. Jeremy Seamans for helpful comments on the manuscript, and Mr. Brain Lowry (University of Pittsburgh) for developing and maintaining the software used to acquire and analyze electrophysiological recordings (Neuroscope). This work was supported by a NARSAD grant (A.L.) and an Internal grant (URC) from MUSC (A.L.), USPHS

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