Changes in levels of regional CRF-like-immunoreactivity and plasma corticosterone during protracted drug withdrawal in dependent rats (original) (raw)

Abstract.

Rationale: Despite prolonged abstinence, prior drug dependence is accompanied by lasting changes in physiology, psychosocial functioning and vulnerability to relapse. One proposed mechanism for these alterations is dysregulation of corticotropin-releasing factor (CRF) neurocircuitry. Objectives: To determine regional brain CRF content and HPA-axis activity during protracted cocaine and ethanol withdrawal in dependent rats. Methods: To study protracted ethanol withdrawal, rats (_n_=22) were fed a nutritionally complete, ethanol (10% v/v) liquid diet for 3–4 weeks. Controls (_n_=12) were pair-fed an isocaloric, ethanol-free formulation. To study protracted cocaine withdrawal, rats (_n_=23) self-administered cocaine (0.25 mg/infusion; FR-5) daily for 3 weeks during 3-h sessions and subsequently were allowed to self-administer cocaine during two 12-h "binge" sessions. Controls (_n_=6) received yoked saline infusions. Regional brain CRF-like-immunoreactivity (CRF-LI), plasma ACTH-LI and CORT-LI levels were determined from 1 day to 6 weeks post-withdrawal. Results: Both ethanol- and cocaine-withdrawn rats initially exhibited reduced CRF-LI content in the amygdala followed by a progressive increase culminating in elevated levels 6 weeks post-withdrawal. Ethanol-withdrawn rats also initially had reduced hippocampal, frontal cortical and hypothalamic CRF-LI levels and time-dependent reductions in basal CORT levels. Cocaine-withdrawn rats showed time-dependent elevations in frontal cortical CRF-LI and basal CORT levels. Conclusions: Protracted withdrawal from ethanol or cocaine is associated with altered limbic CRF-LI and circulating CORT levels beyond the detoxification stage. The delayed nature of some changes suggests that they may not represent residual effects of acute withdrawal, but rather emerging manifestations of a separate process, such as allostatic load.

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  1. CVN7, Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, , , , ,
    Eric P. Zorrilla, Glenn R. Valdez & Friedbert Weiss

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  1. Eric P. Zorrilla
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  2. Glenn R. Valdez
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  3. Friedbert Weiss
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Zorrilla, E.P., Valdez, G.R. & Weiss, F. Changes in levels of regional CRF-like-immunoreactivity and plasma corticosterone during protracted drug withdrawal in dependent rats.Psychopharmacology 158, 374–381 (2001). https://doi.org/10.1007/s002130100773

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