Amphetamine and cocaine do not increase Narp expression in rat ventral tegmental area, nucleus accumbens or prefrontal cortex, but Narp may contribute to individual differences in responding to a novel environment

Eur J Neurosci. 2002 Jun;15(12):2027-36. doi: 10.1046/j.1460-9568.2002.02036.x.

Abstract

Narp is an immediate early gene product that acts extracellularly to cluster AMPA receptors at excitatory synapses. The present study tested the hypothesis that drugs of abuse alter Narp expression and thereby influence AMPA receptor transmission in addiction-related circuits. Immunohistochemical studies demonstrated the existence of Narp-positive cells in hippocampus, prefrontal cortex (PFC) and nucleus accumbens (NAc), with lower levels of staining in the ventral tegmental area (VTA). To study the effects of psychomotor stimulants, Narp levels were quantified by Western blotting and normalized to actin. There were no differences in Narp levels in any brain region between rats treated with repeated saline injections, a single amphetamine injection (5 mg/kg), repeated amphetamine injections (5 mg/kg x 5 days), or repeated cocaine injections (20 mg/kg twice daily x 7 days). We also examined the possible role of Narp in individual differences in responding to a novel environment, a predictor of behavioural responses to psychomotor stimulant drugs including the propensity to acquire drug self-administration. Narp levels in the PFC, but not other regions, were significantly correlated with locomotor activity in a novel environment. These findings suggest that differential Narp expression in the PFC may be involved in determining individual vulnerability to drugs of abuse, perhaps by influencing the activity of its excitatory projections.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amphetamine / pharmacology*
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / physiopathology
  • C-Reactive Protein / drug effects*
  • C-Reactive Protein / metabolism
  • Cocaine / pharmacology*
  • Drug Administration Schedule
  • Drug Tolerance / physiology
  • Exploratory Behavior / drug effects*
  • Exploratory Behavior / physiology
  • Genetic Variation / drug effects
  • Genetic Variation / physiology
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Nerve Tissue Proteins / drug effects*
  • Nerve Tissue Proteins / metabolism
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Nucleus Accumbens / physiopathology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Substance-Related Disorders / metabolism*
  • Substance-Related Disorders / physiopathology
  • Up-Regulation / drug effects*
  • Up-Regulation / physiology
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism
  • Ventral Tegmental Area / physiopathology

Substances

  • Nerve Tissue Proteins
  • neuronal pentraxin
  • C-Reactive Protein
  • Amphetamine
  • Cocaine