Acute and long-term changes in the mesolimbic dopamine pathway after systemic or local single nicotine injections

Eur J Neurosci. 2002 Jun;15(11):1810-8. doi: 10.1046/j.1460-9568.2001.02009.x.


We have examined several neurochemical and behavioural parameters related to the function of the mesolimbic dopamine (DA) pathway in animals treated with nicotine following three modes of drug administration, i.e. systemic intraperitoneal injection, intra-accumbens (Acb) infusion or intraventral tegmental area (intra-VTA) microinjection. The present modes of systemic, intra-Acb and intra-VTA nicotine administration elicited comparable acute increases in dialysate DA levels from the Acb. The increase in extracellular DA levels was paralleled by a significant enhancement of locomotion in a habituated environment in the case of systemic or intra-VTA nicotine administration, whereas unilateral or bilateral intra-Acb nicotine infusion was ineffective, showing that accumbal DA increase is not sufficient to elicit locomotion in this experimental paradigm. Intra-VTA, but not systemic or intra-Acb, nicotine administration caused a long-term (at least 24-h) increase in basal dialysate DA levels from the Acb. In addition, significant increases in tyrosine hydroxylase (TH) and GluR1 (but not dopamine transporter or NR1) mRNA levels in the VTA were detected 24 h after intra-VTA nicotine administration. Systemic nicotine injection caused only an increase in TH mRNA levels while intra-Acb infusion did not modify any of the mRNAs tested. The long-term increase in basal DA levels in the Acb and TH, and GluR1 mRNA levels in the VTA upon intra-VTA nicotine microinjection indicates that even a single nicotine injection can induce plastic changes of the mesolimbic DA pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / pharmacology
  • Animals
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Drug Administration Routes
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Habituation, Psychophysiologic / drug effects
  • Habituation, Psychophysiologic / physiology
  • Male
  • Membrane Glycoproteins*
  • Membrane Transport Proteins / genetics
  • Microdialysis
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Nerve Tissue Proteins*
  • Neural Pathways / drug effects*
  • Neural Pathways / metabolism
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / physiology
  • Nicotine / pharmacology*
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Presynaptic Terminals / drug effects*
  • Presynaptic Terminals / metabolism
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / genetics
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Substance-Related Disorders / metabolism
  • Substance-Related Disorders / physiopathology
  • Time Factors
  • Tyrosine 3-Monooxygenase / genetics
  • Ventral Tegmental Area / drug effects*
  • Ventral Tegmental Area / metabolism


  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • NR1 NMDA receptor
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Nicotine
  • Amphetamine
  • Tyrosine 3-Monooxygenase
  • glutamate receptor ionotropic, AMPA 1
  • Dopamine