The decreased cyclic-AMP dependent-protein kinase A function in the nucleus accumbens: a role in alcohol drinking but not in anxiety-like behaviors in rats.
The nucleus accumbens (NAc) brain structures have been implicated in the reward and reinforcing properties of ethanol. The present study investigated the role of nucleus accumbal cyclic AMP (cAMP)-dependent protein kinase A (PKA) signaling in alcohol drinking and anxiety-like behaviors of rats. It was found that infusion of PKA inhibitor (Rp-cAMP) into the NAc shell significantly increased the alcohol but not the sucrose intake, without modulating the anxiety-like behaviors, as measured by elevated plus maze test in rats. PKA inhibitor infusion into the NAc shell significantly decreased the protein levels of alpha-catalytic subunit of PKA (PKA-Calpha) and phosphorylated cAMP response element-binding protein (p-CREB) as well as decreased the protein levels of neuropeptide Y (NPY) in the shell but not in the NAc core of rats. On the other hand, infusion of PKA activator (Sp-cAMP) or NPY alone into the NAc shell did not produce any changes in alcohol intake; however, when these agents were coinfused with PKA inhibitor, they significantly attenuated the increases in alcohol preference induced by pharmacological inhibition of PKA. Interestingly, PKA activator coinfusion with PKA inhibitor into the NAc shell significantly normalized the PKA inhibitor-induced decreases in the protein levels of PKA-Calpha and p-CREB as well as of NPY in the NAc shell of rats. Taken together, these results provide the first evidence that decreased PKA function in the NAc shell is involved in alcohol drinking but not in anxiety-like behaviors of rats. Furthermore, decreased function of PKA may regulate alcohol drinking behaviors via CREB-mediated decreased expression of NPY in the NAc shell of rats.
Misra
Kaushik
K
Department of Psychiatry, University of Illinois at Chicago, Jesse Brown VA Medical Center, Chicago, IL 60612, USA.
Pandey
Subhash C
SC
D000428:Alcohol Drinking / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000201:enzymology* / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
D002492:Central Nervous System Depressants; D017362:Cyclic AMP Response Element-Binding Protein; D009478:Neuropeptide Y; D047428:Protein Kinase Inhibitors; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D000431:Ethanol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases