Abstract
The loss of control over cocaine use and persistently heightened susceptibility to drug relapse that define human cocaine addiction are consequences of drug-induced neuroplasticity and can be studied in rats self-administering cocaine under conditions of daily long access (LgA) as escalating patterns of drug intake and heightened susceptibility to reinstatement. This study investigated the potential contribution of elevated glucocorticoids at the time of LgA cocaine self-administration (SA) to these behavioral indices of addiction-related neuroplasticity. Rats provided 14 days of 6-h access (LgA) to cocaine showed a progressive escalation of SA and were more susceptible to cocaine-induced reinstatement (10 mg/kg, i.p.) compared to rats self-administering under short-access (ShA; 2 h) conditions. A surgical adrenalectomy and corticosterone replacement (ADX/C) regimen that eliminated SA-induced increases in corticosterone (CORT) while maintaining the diurnal pattern of secretion failed to alter SA or reinstatement in ShA rats but slowed escalation and attenuated later reinstatement in LgA rats when applied before but not after chronic LgA SA testing. Although the contribution of other adrenal hormones cannot be ruled out, these data suggest that elevated glucocorticoids at the time of cocaine exposure may be required for the effects of LgA SA on cocaine intake and later reinstatement. The inability of daily CORT administration before daily ShA SA, at a dose that reproduced the response during LgA SA, to mimic the effects of LgA SA suggests that elevated glucocorticoids during SA may play a permissive role in cocaine-induced neuroplasticity that contributes to addiction.
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Acknowledgements
This work was supported by National Institute on Drug Abuse (NIDA) grants number DA15758 to JRM and DA017328 to DAB. We thank Tanveer Sajan for her technical assistance and Dr Kristen Kau for her helpful comments on the manuscript.
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The authors declare that they have no conflict of interest related to this report.
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John R Mantsch and David A Baker are affiliated with Promentis Pharmaceuticals.
Joseph P Serge, Michael A Hoks, David M Francis, and Eric S Katz have no other professional affiliation at this time.
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Mantsch, J., Baker, D., Serge, J. et al. Surgical Adrenalectomy with Diurnal Corticosterone Replacement Slows Escalation and Prevents the Augmentation of Cocaine-Induced Reinstatement in Rats Self-Administering Cocaine Under Long-Access Conditions. Neuropsychopharmacol 33, 814–826 (2008). https://doi.org/10.1038/sj.npp.1301464
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DOI: https://doi.org/10.1038/sj.npp.1301464
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