NEUROTROPHINS AND REPEATED COCAINE

Project Details

Description

DESCRIPTION (Adapted From The Applicant's Abstract):
The abuse of amphetamine-like psychostimulants is a global medical and social
problem. The rewarding property of psychostimulants is linked, at least in
part, to the capacity of these drugs to increase extracellular dopamine in the
basal forebrain, notably in the nucleus accumbens. Despite the advances in our
understanding of the cellular and molecular actions of psychostimulants,
effective pharmcological treatments for amphetamine and cocaine addiction
remain elusive. One paradigm, known as behavioral sensitization, models
psychostimulant-induced adaptations in the addict brain by assessing changes in
rodent neuronal function and behavior following repeated, daily injections of
cocaine. Recent data suggests that the neurotrophins promote neural plasticity
in the mesoaccumbens dopamine system and may contribute to behavioral
sensitization. This grant proposal will expand on these initial findings by
assessing potential cellular and molecular mechanisms whereby neurtrophins and
neurotrophin-stimulated second messenger systems influence the ability of
psychostimulants to promote behavioral sensitization. These experiments will
assess: i) the effects of repeated intra-cranial microinjections of
neurotrophins on the behavioral activation induced by a subsequent challenge
injection of cocaine, ii) changes in neurotrophin mRNA in the
mesolimbic/nigrostriatal dopamine system following acute and repeated cocaine,
and iii) alterations in extracellular neurotrophins and dopamine in the cell
body and terminal regions of mesotelencephalic dopamine projections. Further
characterization of the role of the neurotrophins in the behavioral plasticity
associated with repeated cocaine injections will provide valuable new
information that may be relevant to the pharmacological treatment of the
intense drug craving associated with pscyhostimulant withdrawal.
StatusFinished
Effective start/end date9/30/9912/31/04

Funding

  • National Institute on Drug Abuse
  • National Institute on Drug Abuse: $1,773.00
  • National Institute on Drug Abuse: $168,726.00
  • National Institute on Drug Abuse: $159,041.00
  • National Institute on Drug Abuse: $188,338.00

ASJC

  • Psychiatry and Mental health
  • Social Sciences(all)

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