title: Glutamatergic and GABAergic metabolism in mouse brain under chronic nicotine exposure: implications for addiction.
abstract: OBJECTIVE
  The effects of nicotine on cerebral metabolism and its influence on smoking behavior is poorly understood. An understanding of the chronic effects of nicotine on excitatory and inhibitory metabolic demand, and corresponding neurotransmission may provide clues for designing strategies for the optimal smoking cessation intervention. The objective of the current study was to investigate neuronal and astroglial metabolism in mice exposed to nicotine (0.5 and 2.0 mg/kg, s.c.) three times in a day for 4 weeks.
  Metabolic measurements were carried out by co-infusing [U-(13)C(6)]glucose and [2-(13)C]acetate, and monitoring (13)C labeling of amino acids in brain tissue extract using (1)H-[(13)C] and (13)C-[(1)H]-NMR spectroscopy. Concentration of (13)C-labeled glutamate-C4 was increased significantly from glucose and acetate with chronic nicotine treatment indicating an increase in glucose oxidation by glutamatergic neurons in all brain regions and glutamate-glutamine neurotransmitter cycle in cortical and subcortical regions. However, chronic nicotine treatment led to increased labeling of GABA-C2 from glucose only in the cortical region. Further, increased labeling of glutamine-C4 from [2-(13)C]acetate is suggestive of increased astroglial activity in subcortical and cerebellum regions of brain with chronic nicotine treatment.
  
  
  CONCLUSIONS
  Chronic nicotine exposure enhanced excitatory activity in the majority of brain regions while inhibitory and astroglial functions were enhanced only in selected brain regions.
authors: NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology (CCMB), Council of Scientific and Industrial Research (CSIR), Hyderabad, India.
authors: Mohammad
authors: M
authors: Shameem
authors: Anant Bahadur
authors: AB
authors: Patel
mesh_terms: D000085:Acetates / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D019966:Substance-Related Disorders / Q000378:metabolism* / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000085:Acetates; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; D005947:Glucose