Upregulation of voluntary alcohol intake, behavioral sensitivity to stress, and amygdala crhr1 expression following a history of dependence.
Biol Psychiatry
; 63(2): 139-45, 2008 Jan 15.
Article
in En
| MEDLINE
| ID: mdl-17585886
ABSTRACT
BACKGROUND:
A history of alcohol dependence recruits increased voluntary alcohol intake and sensitivity to stress. Corticotropin-releasing hormone (CRH) has been implicated in this transition, but underlying molecular mechanisms remain unclear.METHODS:
A postdependent state was induced using intermittent alcohol exposure. Experiments were carried out following > or =3 weeks of recovery to eliminate contributions of acute withdrawal. Voluntary alcohol consumption was assessed in a two-bottle, free choice procedure. Behavioral sensitivity to stress was examined using fear suppression of behavior in a punished drinking (Vogel) conflict test. Effects of forced swim stress on voluntary alcohol intake were examined as a function of exposure history. Expression of Crh, Crhr1, and Crhr2 transcripts was analyzed by in situ hybridization histochemistry.RESULTS:
Alcohol drinking was upregulated long-term following a history of dependence. Fear suppression of behavior was selectively potentiated in postdependent animals. This persisted 3 months after alcohol exposure and was reversed by the selective CRH-R1 antagonist 3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (MTIP) (10 mg/kg). Forced swim stress increased alcohol intake in postdependent animals but not in control animals. Behavioral changes were paralleled by an upregulation of Crhr1 transcript expression within basolateral (BLA) and medial (MeA) amygdala and Crh messenger RNA (mRNA) in central amygdala (CeA). In contrast, Crhr2 expression was down in the BLA.CONCLUSIONS:
Neuroadaptations encompassing amygdala CRH signaling contribute to the behavioral phenotype of postdependent animals.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stress, Physiological
/
Alcohol Drinking
/
Receptors, Corticotropin-Releasing Hormone
/
Alcoholism
/
Amygdala
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Biol Psychiatry
Year:
2008
Document type:
Article
Affiliation country:
United States