Modulation of cocaine-induced motor activity in the rat by opioid receptor agonists.
Selective opioid-receptor agonists were tested in combination with cocaine to determine the effect on the motor activity of rats. Cocaine produced dose-dependent increases in locomotor activity (distance traveled). The cocaine-induced increase in locomotor activity was potentiated by the selective delta-opioid receptor agonist [D-Pen2-D-Pen5]enkephalin (DPDPE). This potentiation was blocked by the general opioid receptor antagonist naltrexone, as well as by the selective opioid receptor antagonists beta-FNA (mu-opioid receptor) and naltrindole (delta-opioid receptor). DPDPE also potentiated the increase in locomotor activity produced by the selective dopamine reuptake inhibitor GBR12909, but not that produced by the direct dopamine receptor agonist apomorphine. Cocaine-induced motor activity was potentiated by the activation of central delta-opioid receptors. The synergistic effect seen with delta-opioid receptor activation may involve a mu-opioid receptor component, and is probably mediated via a dopaminergic pathway.
Waddell
A B
AB
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Holtzman
S G
SG
D000818:Animals; D002946:Cisterna Magna; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D007267:Injections; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D014179:Neurotransmitter Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology
D003042:Cocaine; D018765:Dopamine Uptake Inhibitors; D005473:Fluoxetine; D014179:Neurotransmitter Uptake Inhibitors; D009638:Norepinephrine; D010879:Piperazines; D011957:Receptors, Opioid; D017367:Selective Serotonin Reuptake Inhibitors; C011386:nisoxetine; C043425:vanoxerine