Sensitization to the behavioral effects of cocaine: modulation by dynorphin and kappa-opioid receptor agonists.
Several lines of evidence suggest an involvement of the mesolimbic dopamine (DA) system in the mediation of psychostimulant-induced sensitization. It is also apparent that endogenous opioid peptide systems can modulate the activity of this same DA system. Psychostimulant-induced alterations in opioid peptide gene expression have also been reported. In this review, evidence will be presented that demonstrates that the administration of kappa-opioid agonists can prevent the initiation of behavioral sensitization to cocaine and that such treatment is also effective in preventing alterations in mesolimbic DA neurotransmission that occur as a consequence of repeated cocaine administration. The putative role of opioid-DA interactions in the modulation of psychostimulant-induced sensitization will also be discussed.
Shippenberg
T S
TS
Brain Imaging Section, NIDA Division of Intramural Research, Baltimore, MD 21224, USA.
Rea
W
W
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004399:Dynorphins / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects*; D017473:Receptors, Opioid, kappa / Q000819:agonists*
D017473:Receptors, Opioid, kappa; D004399:Dynorphins; D003042:Cocaine