Kappa opioid agonists alter dopamine markers and cocaine-stimulated locomotor activity.
To better understand the influence of kappa-opioid agonists on the effects of cocaine, rats were treated with daily injections of the selective kappa-opioid agonist U-69593 or bremazocine. In combination with 10 mg/kg cocaine, both compounds, at a dose of 0.32 mg/kg, greatly diminished locomotor activity, and these effects were maintained over a period of 5 days. In addition, the response to a challenge injection of 10 mg/kg cocaine several days after the end of kappa-Opioid agonist treatment with or without cocaine was markedly reduced. When naltrexone was given in combination with U-69593, it blocked the reduction in cocaine-induced locomotor activity after U-69593 treatment alone. However, a single injection of either kappa-opioid agonist alone had no effect on cocaine-induced locomotion several days later (i.e. no long-term effects), suggesting that multiple injections of the kappa-opioid agonist are needed to reduce the locomotor activating effects of cocaine other than acutely. In addition, treatment with the kappa-opioid agonist U-69593 (0.32 mg/kg) over a 5-day period decreased dopamine transporter densities in the caudate putamen, and this was also blocked by co-administration of naltrexone.
Collins
S L
SL
Department of Neurology, University of Miami School of Medicine, Florida 33136, USA.
Gerdes
R M
RM
D'Addario
C
C
Izenwasser
S
S
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D044482:Benzeneacetamides; D001575:Benzomorphans / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects*; D009271:Naltrexone / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects; D009419:Nerve Tissue Proteins; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*
D000700:Analgesics; D044482:Benzeneacetamides; D001575:Benzomorphans; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D009271:Naltrexone; D003042:Cocaine; C027248:bremazocine; C045444:U 69593; D004298:Dopamine