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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.
- Source :
-
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2006 Jul; Vol. 31 (7), pp. 1406-19. Date of Electronic Publication: 2005 Sep 28. - Publication Year :
- 2006
-
Abstract
- 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.
- Subjects :
- Alcohol Drinking drug therapy
Animals
Anxiety physiopathology
Behavior, Animal drug effects
Central Nervous System Depressants administration & dosage
Cyclic AMP analogs & derivatives
Cyclic AMP pharmacology
Cyclic AMP Response Element-Binding Protein metabolism
Dose-Response Relationship, Drug
Drinking drug effects
Drug Interactions
Ethanol administration & dosage
Immunohistochemistry methods
Male
Maze Learning drug effects
Neuropeptide Y metabolism
Neuropeptide Y pharmacology
Protein Kinase Inhibitors pharmacology
Rats
Rats, Sprague-Dawley
Thionucleotides pharmacology
Time Factors
Alcohol Drinking metabolism
Anxiety enzymology
Cyclic AMP-Dependent Protein Kinases metabolism
Nucleus Accumbens enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 0893-133X
- Volume :
- 31
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 16192983
- Full Text :
- https://doi.org/10.1038/sj.npp.1300900