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Time-dependent recovery from the effects of 6-hydroxydopamine lesions of the rat nucleus accumbens on cocaine self-administration and the levels of dopamine in microdialysates

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Abstract

Rationale

Neurotoxin induced lesions of dopamine-releasing neurons that innervate the nucleus accumbens (NAcc) alter cocaine self-administration. In addition, elevated extracellular levels of NAcc dopamine (DA) are thought to be central to the biological mechanisms that underlie this behavior.

Objectives

This study assessed the long-term effects of 6-hydroxydopamine (6-OHDA) induced lesions of the NAcc on cocaine self-administration and the dialysate levels of dopamine ([DA]d) in this structure to determine if recovery of drug intake was correlated with the DA response.

Methods

Rats implanted with jugular catheters and bilateral cannulas were trained to self-administer cocaine and subsequently received bilateral intracranial micro-injections of 6-OHDA or vehicle into the NAcc. The levels of DA and cocaine were determined in microdialysates of the NAcc collected during experimental sessions 6–7, 14–16, 29–30, and 44–46 days post-treatment.

Results

The 6-OHDA induced lesions significantly reduced cocaine self-administration for 3 weeks while vehicle treatment had a moderate effect for the first several days. Cocaine-induced increases in NAcc [DA]d did not return to sham/vehicle treated control levels for 6 weeks in the lesioned group and DA content in the NAcc was 46% of control at 44 days post-lesion.

Conclusions

Although dopaminergic lesions of the NAcc produced profound effects on cocaine self-administration, responding recovered to control levels before cocaine-induced increases in NAcc [DA]d while content of DA in the NAcc did not recover. These data suggest that the plasticity of neuronal systems in the NAcc related to cocaine self-administration and their response following 6-OHDA lesions is more complex than restoration of DAergic tone.

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Acknowledgements

The conduct of this experiment was consistent with the ethical standards outlined in "Principles of laboratory animal care" (NIH publication No. 80-23, revised 1996). This research was supported by grants from the National Institute on Drug Abuse: DA 03628, DA 06634 and DA00114.

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Authors and Affiliations

  1. Center for the Neurobiological Investigation of Drug Abuse, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA

    Glen M. Sizemore, Conchita Co, Thomas J. Martin & James E. Smith

  2. Department of Physiology, Eastern Carolina University, East Fifth Street, Greenville, NC 27858-4353, USA

    Timothy R. Koves

  3. Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1083, USA

    James E. Smith

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  1. Glen M. Sizemore
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  2. Conchita Co
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  5. James E. Smith
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Correspondence to James E. Smith.

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Sizemore, G.M., Co, C., Koves, T.R. et al. Time-dependent recovery from the effects of 6-hydroxydopamine lesions of the rat nucleus accumbens on cocaine self-administration and the levels of dopamine in microdialysates. Psychopharmacology 171, 413–420 (2004). https://doi.org/10.1007/s00213-003-1596-6

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