Project: Research project

Project Details


Neuropeptide Y (NPY) is a highly bioactive 36-amino acid peptide that
occurs abundantly in brain. In preliminary experiments, we found that
repeated administration of cocaine elicits substantial, long-lasting,
biochemically-selective, and reversible reductions in levels of NPY and
NPY mRNA in regions of rat cerebral cortex and nucleus accumbens.
Excitotoxic lesions of medial prefrontal cortex, a region thought to be
of importance for the expression of some of cocaine's reinforcing
properties, did not affect NPY per se but prevented the reduction of NPY
elicited by cocaine. Thus, it appears that chronic exposure to cocaine
transneuronally reduces, in selected neurons, the biosynthesis of NPY,
possibly in response to increases in synaptic dopamine (DA) deriving from
mesolimbic/mesocortical neurons; the integrity of the medial prefrontal
cortex may be crucial for cocaine's action on this neuronal network. In
this study, we seek to determine regional selectivity and kinetics of
cocaine/NPY interactions. The hypothesis that DA mediates cocaine's
action on transcription of the NPY gene will be tested in vivo and in
vitro. Moreover, the reduction in NPY may be reflected in cerebrospinal
fluid and by an upregulation of NPY receptors. Finally, we will explore
the possibilities that the nucleus accumbens, like the medial prefrontal
cortex, is necessary for the effect, and that gestational and/or neonatal
cocaine exposure affects NPY systems. We propose that NPY may be a
sensitive and selective marker for chronic cocaine use. Its reduction
may relate to the anxiety and depression associated with cocaine
withdrawal in man.
Effective start/end date4/1/913/31/94


  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)


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