NEUROCHEMICAL PATHOLOGY OF HUMAN COCAINE ABUSE

Project: Research project

Project Details

Description

In spite of a plethora of published studies in laboratory animals that
have documented effects of cocaine on specific central nervous system
neurotransmitter systems, there is remarkably little known about the
chronic effects of this psychostimulant on the human brain. In this
proposal we seek to scrutinize the effects of chronic cocaine abuse in
humans by assessment of neurochemical alteration in approximately 50 brain
regions derived from post-mortem brain tissue of confirmed cocaine abusers
(with segmental hair analysis to document the temporal pattern of cocaine
use) and age- and sex-matched controls. Through cocaine's actions on
monoamine transporters, the preclinical literature has clearly implicated
dopamine (DA), serotonin (5MT) and norepinephrine (NE)-containing neurons
in mediating the actions of cocaine; there is also considerable evidence
implicating two neuropeptide neuronal systems (corticotropin-releasing
factor [CRF] and neurotensin [NT]) in the actions of this drug of abuse.
Alterations in the monoamine transporters will be assessed by measurement
of: radioligand binding, transporter protein concentration by the use of
newly developed specific antibodies to the transporters, and mRNA
expression of the transporters. Alterations in CRF and NT systems will be
assessed by measurement of the neuropeptides, neuropeptide mRNA
expression, neuropeptide receptor binding, neuropeptide receptor mRNA
expression, and in the case of the CRF system, the CRF-binding protein and
CRF signal transduction. These studies will provide novel data on the
effects of cocaine abuse on specific neurotransmitter systems in the human
central nervous system.
StatusFinished
Effective start/end date7/1/955/31/99

Funding

  • National Institute on Drug Abuse

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