Neuroadaptive changes in the mesocortical glutamatergic system during chronic nicotine self-administration and after extinction n rats

Fan Wang, Hao Chen, Burt Sharp

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Nicotine self-administration causes adaptation in the meso-corticolimbic glutamatergic system, including the up-regula-tion 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 μM NMDA, KRB, 500 μM NMDA, KRB, and 100 mM KCI. Basal glutamate levels were unaffected, but nicotine self-administration significantly potentiated mPFC glutamate release to 200 μM NMDA, which was ineffective in controls. Furthermore, in VTA, nicotine self-administration significantly ampli-fied 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.

Original languageEnglish (US)
Pages (from-to)943-956
Number of pages14
JournalJournal of Neurochemistry
Volume106
Issue number2
DOIs
StatePublished - Jul 1 2008

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Self Administration
Nicotine
Rats
Glutamic Acid
N-Methylaspartate
Prefrontal Cortex
Ventral Tegmental Area
Synaptic Transmission
Buffers
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Sucrose
2-Amino-5-phosphonovalerate
Ionotropic Glutamate Receptors
Microinjections
Maintenance

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

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title = "Neuroadaptive changes in the mesocortical glutamatergic system during chronic nicotine self-administration and after extinction n rats",
abstract = "Nicotine self-administration causes adaptation in the meso-corticolimbic glutamatergic system, including the up-regula-tion 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 μM NMDA, KRB, 500 μM NMDA, KRB, and 100 mM KCI. Basal glutamate levels were unaffected, but nicotine self-administration significantly potentiated mPFC glutamate release to 200 μM NMDA, which was ineffective in controls. Furthermore, in VTA, nicotine self-administration significantly ampli-fied 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.",
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