Corticotropin-releasing factor overexpression decreases ethanol drinking and increases sensitivity to the sedative effects of ethanol.
BACKGROUND
Corticotropin-releasing factor (CRF) may play a significant role in drug and alcohol abuse.


OBJECTIVE
To evaluate the role of CRF in these processes, we examined several ethanol (EtOH) related behaviors in mice that carry a transgene that causes overexpression of CRF.


METHODS
We examined voluntary EtOH drinking, loss of the righting reflex (LORR), EtOH-induced conditioned taste aversion (CTA), and EtOH clearance in littermate transgenic (TG) and non-transgenic (non-TG) mice. In addition, because preliminary results indicated that age exacerbated differences in EtOH consumption between the two genotypes, we performed a cross-sectional and longitudinal evaluation of this trait at two ages ( approximately 100 and 200 days old).


RESULTS
We found that TG mice consumed significantly less EtOH and had a lower preference for EtOH-containing solutions compared with their non-TG littermates. We also found that the older drug-naive TG mice drank less EtOH as compared with the younger mice of the same genotype; however, the same relationship did not exist for drug-naive non-TG mice. Prior experience in drinking EtOH when 100 days old led to decreased EtOH drinking when 200 days old in both genotypes. Duration of LORR was longer in the TG mice, EtOH-induced CTA was marginally greater in non-TG mice at the highest dose tested, and there were significant but small differences in EtOH clearance parameters.


CONCLUSIONS
These data show that CRF overexpressing mice voluntarily consume less EtOH. This difference is associated with greater sensitivity to the sedative-hypnotic effects of EtOH, but not with increased sensitivity to the aversive effects of EtOH.
Palmer
Abraham A
AA
Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 Sam Jackson Park Road, Portland, OR 97239, USA.
Sharpe
Amanda L
AL
Burkhart-Kasch
Sue
S
McKinnon
Carrie S
CS
Coste
Sarah C
SC
Stenzel-Poore
Mary P
MP
Phillips
Tamara J
TJ
D000375:Aging / Q000523:psychology; D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D004856:Postural Balance / Q000187:drug effects; D011803:Quinine / Q000494:pharmacology; D012018:Reflex / Q000187:drug effects; D012439:Saccharin / Q000494:pharmacology; D013649:Taste / Q000187:drug effects
D002492:Central Nervous System Depressants; D000431:Ethanol; D003346:Corticotropin-Releasing Hormone; D011803:Quinine; D012439:Saccharin