¹Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN, USA

Correspondence: Dr BM Sharp, Department of Pharmacology, University of Tennessee Health Science Center, Suite 115 Crowe Building, 874 Union Avenue, Memphis, TN 38163 USA. Tel: +1 901 448 6000; Fax: +1 901 448 7206; E-mail: bsharp@utmem.edu

Received 4 May 2005; Revised 4 November 2005; Accepted 19 December 2005; Published online 1 February 2006.

Abstract

Nicotine, an addictive substance, is the major psychoactive component in cigarette smoke. Both -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate (NMDA) receptors are essential for the acute stimulative effects of nicotine on the mesocorticolimbic dopamine system, yet little is known about the effects of chronic nicotine treatment on glutamate receptors. Therefore, we used a model of chronic nicotine self-administration (SA), which emulates important aspects of nicotine intake by humans, to determine whether glutamate receptor subunits were affected. After 18 days of saline vs nicotine SA, ionotropic glutamate receptor subunit levels were determined in brain regions within the mesocorticolimbic system by Western blotting. In prefrontal cortex (PFC), the levels of NMDA receptor subunit 2A (NR2A) and NR2B were increased by 67% (p=0.04) and 83% (p=0.027), respectively. In the ventral tegmental area (VTA), glutamate receptor subunit 2/3 (GluR2/3) increased by 34% (p=0.011). Nicotine SA did not affect the expression of these subunits in dorsal striatum and nucleus accumbens. These findings suggest that chronic nicotine SA selectively increased the levels of ionotropic glutamate receptor subunits in a brain region-specific manner.