Chronic nicotine and smoke treatment modulate dopaminergic activities in ventral tegmental area and nucleus accumbens and the gamma-aminobutyric acid type B receptor expression of the rat prefrontal cortex

J Neurosci Res. 2004 Dec 15;78(6):868-79. doi: 10.1002/jnr.20329.


Dopaminergic afferents from the mesencephalic areas, such as ventral tegmental area (VTA), synapse with the gamma-aminobutyric acid (GABA)-ergic interneurons in the prefrontal cortex (PFC). Pharmacological and electrophysiological data show that the reinforcement, the dependence-producing properties, as well as the psychopharmacologic effects of nicotine depend to a great extent on activation of nicotinic receptors within the mesolimbocortical dopaminergic projection. To explore further the relationship between the mesencephalic dopaminergic neurons and PFC GABAergic neurons, we investigated the effects of nicotine and passive exposure to cigarette smoke on the regulation of tyrosine hydroxylase (TH) in VTA and substantia nigra (SNC) and dopamine (DA) D1 receptor levels in nucleus accumbens (NAc) and caudate-putamen (CPu). Also, the simultaneous changes in GABAB receptors mRNAs in the PFC were studied. The results showed that chronic nicotine and smoking treatment differentially changed the levels of TH protein in VTA and SNC and DA D1 receptor levels in Nac and CPu. GABAB1 and GABAB2 receptor mRNA levels also showed different change patterns. Ten and thirty minutes of smoke exposure increased GABAB1 receptor mRNA to a greater extent than that of GABAB2, whereas GABAB2 was greatly enhanced after 1 hr of smoke exposure. The TH levels in VTA were closely related to DA D1 receptor levels in NAc and with GABAB receptor mRNA changes in PFC. These results suggest that the mesolimbic pathway and GABAB receptor mRNA in PFC are modulated by nicotine and cigarette smoke, implying an important role in nicotine's psychopharmacological effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Dopamine / physiology*
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Nicotine / pharmacology*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiology*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology*
  • RNA, Complementary
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-B / drug effects
  • Receptors, GABA-B / genetics*
  • Smoke / adverse effects*
  • Tegmentum Mesencephali / drug effects
  • Tegmentum Mesencephali / physiology*


  • RNA, Complementary
  • Receptors, GABA-B
  • Smoke
  • Nicotine
  • Dopamine