Modulation of brain endocannabinoid levels by voluntary alcohol consumption in alcohol-preferring AA rats.
BACKGROUND
The central nervous system cannabinoid CB1 receptors have been implicated in regulation of alcohol consumption. Less data are available on the role of the endogenous ligands for these receptors, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), in alcohol-related behaviors. The purpose of this study was to assess the effects of voluntary alcohol consumption on the levels of these endocannabinoids in key brain areas mediating alcohol reinforcement.


METHODS
Female and male alcohol-preferring AA (Alko, Alcohol) rats were trained to drink 10% (v/v) alcohol during 90-min limited access sessions every second day. Following establishment of stable alcohol drinking, half of the subjects were killed immediately before the daily alcohol access ("pre-session" group), while the other half was killed after the drinking session ("post-session" group). A separate control group consisted of water-drinking rats. AEA and 2-AG levels were measured from prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CPu), amygdala, and hippocampus using liquid chromatography-tandem mass spectrometry (LC/MS/MS).


RESULTS
Voluntary alcohol drinking caused widespread alterations in the levels of both AEA and 2-AG. Compared to the water group, increased AEA levels were seen in the pre-session group, but they were decreased immediately following limited access drinking in the female AA rats. Also 2-AG levels were significantly elevated after long alcohol exposure, and an additional increase was found after limited access drinking in PFC. In males, however, the only alterations caused by alcohol drinking were significantly elevated AEA levels in NAc and CPu in the post-session group. No changes were seen in the levels of 2-AG.


CONCLUSIONS
These results demonstrate that voluntary alcohol drinking modulates the levels of endocannabinoids in several brain areas implicated in alcohol reinforcement. AEA and 2-AG were differentially affected, suggesting that they could have partially separate modulatory roles. Alterations were more widespread in females than males, possibly reflecting their higher alcohol intake. Taken together, alcohol-induced release of endocannabinoids may have an important role in alcohol reinforcement and development of alcohol addiction.
Malinen
Hanna
H
National Institute for Health and Welfare, Helsinki, Finland.
Lehtonen
Marko
M
Hyytiä
Petri
P
D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism* / Q000523:psychology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003627:Data Interpretation, Statistical; D063388:Endocannabinoids; D030762:Estrous Cycle / Q000187:drug effects / Q000235:genetics; D005260:Female; D008297:Male; D051381:Rats; D012015:Reference Standards; D013549:Sweetening Agents / Q000494:pharmacology; D053719:Tandem Mass Spectrometry; D013649:Taste / Q000235:genetics / Q000502:physiology
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D013549:Sweetening Agents