The CRF-1 receptor antagonist, CP-154,526, attenuates stress-induced increases in ethanol consumption by BALB/cJ mice.
BACKGROUND
Corticotropin-releasing factor (CRF) signaling modulates neurobiological responses to stress and ethanol, and may modulate observed increases in ethanol consumption following exposure to stressful events. The current experiment was conducted to further characterize the role of CRF1 receptor (CRF1R) signaling in stress-induced increases in ethanol consumption in BALB/cJ and C57BL/6N mice.


METHODS
Male BALB/cJ and C57BL/6N mice were given continuous access to 8% (v/v) ethanol and water for the duration of the experiment. When a baseline of ethanol consumption was established, animals were exposed to 5 minutes of forced swim stress on each of 5 consecutive days. Thirty minutes before each forced swim session, animals were given an intraperitoneal injection of a 10 mg/kg dose of CP-154,526, a selective CRF1R antagonist, or an equal volume of vehicle. The effect of forced swim stress exposure on consumption of a 1% (w/v) sucrose solution was also investigated in an ethanol-naïve group of BALB/cJ mice.


RESULTS
Exposure to forced swim stress significantly increased ethanol consumption by the BALB/cJ, but not of the C57BL/6N, mice. Stress-induced increases in ethanol consumption were delayed and became evident approximately 3 weeks after the first stressor. Additionally, forced swim stress did not cause increases of food or water intake and did not promote delayed increases of sucrose consumption. Importantly, BALB/cJ mice pretreated with the CRF1R antagonist showed blunted stress-induced increases in ethanol intake, and the CRF1R antagonist did not influence the ethanol drinking of non-stressed mice.


CONCLUSIONS
The present results provide evidence that CRF1R signaling modulates the delayed increase of ethanol consumption stemming from repeated exposure to a stressful event in BALB/cJ mice.
Lowery
Emily G
EG
Department of Psychology, University of North Carolina, Chapel Hill, North Carolina 27599-3270, USA.
Sparrow
Angela M
AM
Breese
George R
GR
Knapp
Darin J
DJ
Thiele
Todd E
TE
D000428:Alcohol Drinking / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013045:Species Specificity; D013315:Stress, Psychological / Q000150:complications*; D000099052:CRF Receptor, Type 1
C101628:CP 154526; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1