Ethanol activates cAMP response element-mediated gene expression in select regions of the mouse brain.
The specific brain regions that contribute to behavioral changes produced by ethanol are not clearly understood. We know that cAMP-PKA signaling has been strongly implicated in the CNS effects of ethanol. Ethanol promotes activation and translocation of the PKA catalytic subunit (Calpha) into the nucleus in cell lines and primary neuronal cultures. PKA Calpha translocation to the nucleus is followed by cAMP Response Element protein phosphorylation (pCREB) and cAMP Response Element (CRE)-mediated gene expression. Here, we use X-gal histochemistry to map CRE-mediated gene transcription in the brain of CRE-lacZ transgenic mice following ethanol injection.


RESULTS
3 h after i.p. ethanol injection (3.2 g/kg, 16% wt/vol.), the number of X-gal positive cells was increased in the nucleus accumbens (202 +/- 63 cells/field compared to 71 +/- 47 cells/field in saline injected controls, P < 0.05 by paired t-test, n = 10). Similar increases were found in other mesolimbic areas and brain regions associated with rewarding and addictive responses. These include: prefrontal cortex, lateral and medial septum, basolateral amygdala, paraventricular and anterior hypothalamus, centromedial thalamus, CA1 region of hippocampus and dentate gyrus, substantia nigra pars compacta, ventral tegmental area, geniculate nucleus and the superior colliculus.


CONCLUSIONS
these results confirm and extend current concepts that ethanol stimulates cAMP-PKA signaling in brain regions involved in CNS responses to ethanol.
Asyyed
Asma
A
Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, 5858 Horton St., Ste. 200, Emeryville, CA 94608, USA. Electronic address: aasyyed@hotmail.com.
Storm
Daniel
D
Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.
Diamond
Ivan
I
Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, 5858 Horton St., Ste. 200, Emeryville, CA 94608, USA; Department of Neuroscience, CV Therapeutics, Palo Alto, CA 94304, USA.
D020268:Alcohol-Induced Disorders, Nervous System / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005697:Galactosides; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D017930:Genes, Reporter / Q000187:drug effects / Q000502:physiology; D007211:Indoles; D007763:Lac Operon / Q000187:drug effects / Q000235:genetics; D008032:Limbic System / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D012201:Reward; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D002492:Central Nervous System Depressants; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D005697:Galactosides; D007211:Indoles; D012333:RNA, Messenger; D000431:Ethanol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside