Alcohol increases the expression of type 1, but not type 2 alpha corticotropin-releasing factor (CRF) receptor messenger ribonucleic acid in the rat hypothalamus.
We investigated the ability of a moderately intoxicating dose of alcohol (3 g/kg, injected i.p. 3 h earlier) to up-regulate the genetic expression of CRF receptor type 1 (CRF-R1) and 2 (CRF-R2alpha) in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus as well as in the amygdala. The mRNA encoding CRF-R1 was not constitutively expressed in the PVN or the SON but was present in the amygdala. Alcohol selectively up-regulated CRF-R1 transcripts in the PVN. Basal levels of CRF-R2alpha transcripts were present in the limbic system and the ventromedial hypothalamic nucleus but were not altered by alcohol. We then determined whether the up-regulation of hypothalamic CRF-R1 mRNA levels was functionally connected to CRF-dependent pathways. We first showed that the i.c.v. injection of CRF significantly (P < 0.01) increased CRF-R1 but not CRF-R2alpha mRNA levels. We then injected the CRF antagonist, astressin, i.c.v. 30 min prior to alcohol, at a dose previously shown to completely block many CRF-dependent events in the brain, and found that it did not significantly interfere with-alcohol-induced gene expression of PVN CRF-R1. These results indicate that acute alcohol treatment selectively activates CRF-R1 in the endocrine hypothalamus and that this response does not appear to depend on the stimulation of CRF receptors. In contrast, no up-regulation of CRF-R1 or CRF-R2alpha gene expression was observed in extrahypothalamic regions thought to participate in the behavioral influence of alcohol.
Lee
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Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, CA 92037, USA.
Rivier
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D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000235:genetics*
D010446:Peptide Fragments; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; C104416:astressin; D000431:Ethanol; D003346:Corticotropin-Releasing Hormone