title: Neuroadaptive changes in the mesocortical glutamatergic system during chronic nicotine self-administration and after extinction in rats.
abstract: Nicotine self-administration causes adaptation in the mesocorticolimbic glutamatergic system, including the up-regulation of ionotropic glutamate receptor subunits. We therefore determined the effects of nicotine self-administration and extinction on NMDA-induced glutamate neurotransmission between the medial prefrontal cortex (mPFC) and ventral tegmental area (VTA). On day 19 of nicotine SA, both regions were microdialyzed for glutamate while mPFC was sequentially perfused with Kreb's Ringer buffer (KRB), 200 microM NMDA, KRB, 500 microM NMDA, KRB, and 100 mM KCl. Basal glutamate levels were unaffected, but nicotine self-administration significantly potentiated mPFC glutamate release to 200 microM NMDA, which was ineffective in controls. Furthermore, in VTA, nicotine self-administration significantly amplified glutamate responses to both mPFC infusions of NMDA. This hyper-responsive glutamate neurotransmission and enhanced glutamate subunit expression were reversed by extinction. Behavioral studies also showed that a microinjection of 2-amino-5-phosphonopentanoic acid (NMDA-R antagonist) into mPFC did not affect nicotine or sucrose self-administration. However, in VTA, NBQX (AMPA-R antagonist) attenuated both nicotine and sucrose self-administration. Collectively, these studies indicate that mesocortical glutamate neurotransmission adapts to chronic nicotine self-administration and VTA AMPA-R may be involved in the maintenance of nicotine self-administration.
authors.affiliation: Department of Pharmacology, University of Tennessee Health Science Center, Memphis, Tennesse, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Burt M
authors.initials: BM
authors.lastname: Sharp
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry / Q000379:methods; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D011189:Potassium Chloride / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D012646:Self Administration; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018683:Excitatory Amino Acid Agents; D018722:Nicotinic Agonists; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D011189:Potassium Chloride; D009538:Nicotine; D015763:2-Amino-5-phosphonovalerate