Adolescent rats are resistant to adaptations in excitatory and inhibitory mechanisms that modulate mesolimbic dopamine during nicotine withdrawal

J Neurochem. 2012 Nov;123(4):578-88. doi: 10.1111/j.1471-4159.2012.07926.x. Epub 2012 Oct 1.


Adolescent smokers report enhanced positive responses to tobacco and fewer negative effects of withdrawal from this drug than adults, and this is believed to propel higher tobacco use during adolescence. Differential dopaminergic responses to nicotine are thought to underlie these age-related effects, as adolescent rats experience lower withdrawal-related deficits in nucleus accumbens (NAcc) dopamine versus adults. This study examined whether age differences in NAcc dopamine during withdrawal are mediated by excitatory or inhibitory transmission in the ventral tegmental area (VTA) dopamine cell body region. In vivo microdialysis was used to monitor extracellular levels of glutamate and gamma-aminobutyric acid (GABA) in the VTA of adolescent and adult rats experiencing nicotine withdrawal. In adults, nicotine withdrawal produced decreases in VTA glutamate levels (44% decrease) and increases in VTA GABA levels (38% increase). In contrast, adolescents did not exhibit changes in either of these measures. Naïve controls of both ages did not display changes in NAcc dopamine, VTA glutamate, or VTA GABA following mecamylamine. These results indicate that adolescents display resistance to withdrawal-related neurochemical processes that inhibit mesolimbic dopamine function in adults experiencing nicotine withdrawal. Our findings provide a potential mechanism involving VTA amino acid neurotransmission that modulates age differences during withdrawal.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptation, Physiological / drug effects
  • Adaptation, Physiological / physiology*
  • Age Factors
  • Analysis of Variance
  • Animals
  • Chromatography, High Pressure Liquid
  • Dialysis
  • Dopamine / metabolism*
  • Electrochemistry
  • Glutamic Acid / metabolism
  • Limbic System / drug effects
  • Limbic System / metabolism*
  • Male
  • Mecamylamine / pharmacology
  • Nicotine / adverse effects*
  • Nicotinic Agonists / adverse effects*
  • Nicotinic Antagonists / pharmacology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Rats
  • Rats, Wistar
  • Statistics as Topic
  • Substance Withdrawal Syndrome / pathology*
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism
  • gamma-Aminobutyric Acid / metabolism


  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Mecamylamine
  • Nicotine
  • Dopamine