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. 2010 Jul 11;210(2):288-91.
doi: 10.1016/j.bbr.2010.02.043. Epub 2010 Mar 1.

Corticotropin-releasing factor mediates the dysphoria-like state associated with alcohol withdrawal in rats

Adrie W Bruijnzeel  1 , Elysia Small, Tim M Pasek, Hidetaka Yamada
Affiliations

Corticotropin-releasing factor mediates the dysphoria-like state associated with alcohol withdrawal in rats

Adrie W Bruijnzeel et al. Behav Brain Res. .

Abstract

This study investigated the role of CRF in the dysphoria-like state associated with alcohol withdrawal in rats. The intracranial self-stimulation procedure was used to assess brain reward thresholds. Cessation of chronic alcohol administration led to an elevation in brain reward thresholds in the alcohol dependent rats. The CRF receptor antagonist D-Phe CRF((12-41)) dose-dependently prevented the elevations in brain reward thresholds associated with alcohol withdrawal. This indicates that the dysphoria associated with alcohol withdrawal is at least partly mediated by the activation of central CRF receptors.

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Figures

Fig. 1
Fig. 1. Timeline experimental procedures
Experimental protocol. Rats were exposed to the alcohol diet from week 0 to week 15 with the exception of the 9-hour withdrawal sessions. Abbreviations: Alc, alcohol; Conc., concentration; ICSS, intracranial self-stimulation; Introd., introduction; W, week; With, withdrawal session. Asterisks (*) indicate when blood samples were collected to determine blood alcohol levels.
Fig. 2
Fig. 2
Effect of the CRF receptor antagonist D-Phe CRF(12-41) (control, n = 20; alcohol, n = 16) on the elevations in brain reward thresholds (A) and increased response latencies (B) associated with alcohol withdrawal. Brain reward thresholds and response latencies are expressed as a percentage of the pretest day values. Crosses (# P<0.05, ## P<0.01) indicate elevations in brain reward thresholds or increased response latencies compared to those of the corresponding control group. Plus signs (+ P<0.05, ++ P<0.01) indicate lower brain reward thresholds compared to those of rats withdrawing from alcohol and acutely treated with vehicle. Asterisks (** P<0.01) indicate lower brain reward thresholds compared to those of rats withdrawing from alcohol and acutely treated with 10 μg of D-Phe CRF(12-41).
Fig. 2
Fig. 2
Effect of the CRF receptor antagonist D-Phe CRF(12-41) (control, n = 20; alcohol, n = 16) on the elevations in brain reward thresholds (A) and increased response latencies (B) associated with alcohol withdrawal. Brain reward thresholds and response latencies are expressed as a percentage of the pretest day values. Crosses (# P<0.05, ## P<0.01) indicate elevations in brain reward thresholds or increased response latencies compared to those of the corresponding control group. Plus signs (+ P<0.05, ++ P<0.01) indicate lower brain reward thresholds compared to those of rats withdrawing from alcohol and acutely treated with vehicle. Asterisks (** P<0.01) indicate lower brain reward thresholds compared to those of rats withdrawing from alcohol and acutely treated with 10 μg of D-Phe CRF(12-41).
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References

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    1. Bruijnzeel AW, Gold MS. The role of corticotropin-releasing factor-like peptides in cannabis, nicotine, and alcohol dependence. Brain Res Brain Res Rev. 2005;49:505–528. - PubMed
    1. Bruijnzeel AW, Prado M, Isaac S. Corticotropin-Releasing Factor-1 Receptor Activation Mediates Nicotine Withdrawal-Induced Deficit in Brain Reward Function and Stress-Induced Relapse. Biol Psychiatry. 2009;66:110–117. - PMC - PubMed
    1. Bruijnzeel AW, Zislis G, Wilson C, Gold MS. Antagonism of CRF receptors prevents the deficit in brain reward function associated with precipitated nicotine withdrawal in rats. Neuropsychopharmacology. 2007;32:955–963. - PubMed

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