Chronic ethanol intake-induced changes in open-field behavior and calcium/calmodulin-dependent protein kinase IV expression in nucleus accumbens of rats: naloxone reversal.
OBJECTIVE
To investigate the effects of chronic ethanol intake on the locomotor activity and the levels of calcium/calmodulin-dependent protein kinase IV (CaM kinase IV) in the nucleus accumbens (NAc) of rats. Simultaneously, the effects of nonselective opioid antagonist (naloxone) on the CaM kinase IV expression in the NAc and ethanol consumption of rats were also observed.


METHODS
Ethanol was administered in drinking water at the concentrations of 6% (v/v), for 28 d. The locomotor activity of rats was investigated in the open-field apparatus. CaM kinase IV levels in the NAc were analyzed using Western blotting.


RESULTS
Rats consuming ethanol solution exhibited a significant decrease of ambulation activity, accompanied by a reduced frequency of explorative rearing in an open-field task on d 7 and d 14 of chronic ethanol ingestion, whereas presumed adaptation to the neurological effects of ethanol was observed on d 28. Chronic ethanol intake elicited a significant decrease of the CaM kinase IV expression in the nuclei, but not in the cytoplasm of the NAc on d 28. Naloxone treatment significantly attenuated ethanol intake of rats and antagonized the decrease of CaM kinase IV in the nuclei of NAc neurons. The cytosolic CaM kinase IV protein levels of the NAc also increased in rats exposed to ethanol plus naloxone.


CONCLUSIONS
Chronic ethanol intake-induced changes in explorative behavior is mediated at least partly by changes in CaM kinase IV signaling in the nuclei of the NAc, and naloxone attenuates ethanol consumption through antagonizing the downregulation of CaM kinase IV in the NAc.
Li
Jing
J
Department of Pathophysiology, Nanjing Medical University, Nanjing 210029, China.
Bian
Wei-liang
WL
Xie
Gui-qin
GQ
Cui
Sheng-zhong
SZ
Wu
Mei-ling
ML
Li
Yue-hua
YH
Que
Ling-li
LL
Yuan
Xiao-ru
XR
D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000096:biosynthesis*; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D009292:Narcotic Antagonists; D009270:Naloxone; D000431:Ethanol; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4