Project Details


The primary thesis of this research proposal is that the central nervous
system alterations that underlie drug taking behaviors involve long-term
adaptive phenomena, both within-systems adaptations and between-systems
adaptations. Thus, an analysis of drug effects that includes but also
extends beyond the primary action of the drug will be fruitful in
furthering our understanding of the cellular aspects of drug abuse.
Within this framework, we propose a thorough analysis of the effects of
amphetamine, a highly abused psychomotor stimulant, upon the
neurochemistry of a circuit that includes basal ganglia and associated
thalamocortical structures. This circuit potentially is capable of
strong influence over psychomotor behaviors. Since the primary action of
amphetamine in brain is the release of the neurotransmitter dopamine, the
hypothesized within-systems adaptations in this circuit would involve
dopamine neurons directly whereas between-systems adaptations would
extend to the neurochemical circuits in which dopamine operates. The
present experiments make use of the technique of in vivo microdialysis to
monitor, in behaving rats, the extracellular concentration of the
neurotransmitters dopamine and acetylcholine at several points in this
circuit First, we propose to document the impact of amphetamine upon
striatal dopamine/acetylcholine dynamics. We will extend our analysis to
include the effects of amphetamine on the release of extra-striatal
dopamine in substantia nigra pars reticulata and in medial prefrontal
cortex. It is hypothesized that amphetamine-induced alterations in
dopamine release in these latter structures may influence striatal
neurochemistry indirectly by affecting the activity of the
corticostriatal glutamatergic pathway. Finally, we will incorporate
these findings into an analysis of neurochemical adaptations in basal
ganglia circuitry in response to repeated amphetamine administration.
The results will provide basic information regarding neurochemical
interactions in the basal ganglia and also will reveal how these
interactions are altered by amphetamine abuse. Such an understanding
surely will provide insight into novel strategies for intervention in the
pharmacological treatment of drug abuse.
Effective start/end date2/1/931/31/99


  • National Institute on Drug Abuse


  • Psychiatry and Mental health
  • Neuroscience(all)


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