¹Department of Psychiatry, Anatomy and Cell Biology, University of Illinois at Chicago and Jesse Brown VA Medical Center, Chicago, IL, USA

Correspondence: Dr SC Pandey, Department of Psychiatry, University of Illinois at Chicago and Jesse Brown VA Medical Center, 820 South Damen Avenue (M/C 151), Chicago, IL 60612, USA. Tel: +1 312 569 7418; Fax: +1 312 569 8114; E-mail: scpandey@uic.edu

Received 31 January 2005; Revised 12 July 2005; Accepted 15 August 2005; Published online 28 September 2005.

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 -catalytic subunit of PKA (PKA-C) 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-C 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.