title: Upregulation of ionotropic glutamate receptor subunits within specific mesocorticolimbic regions during chronic nicotine self-administration.
abstract: Nicotine, an addictive substance, is the major psychoactive component in cigarette smoke. Both alpha-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.
authors.affiliation: Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Steketee
authors.forename: Burt M
authors.initials: BM
authors.lastname: Sharp
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D008032:Limbic System / Q000187:drug effects*; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D017397:Prefrontal Cortex / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012646:Self Administration / Q000379:methods; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D018722:Nicotinic Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D009538:Nicotine