Cocaine: evidence for NMDA- and opioid-mediated antinociception in the tail-flick test.
Cocaine (20-40 mg/kg, IP) produced in a rat tail-flick test a bimodal antinociceptive effect, the first peak appearing 5-30 min and the second 3-6 h after injection. The secondary, but not the initial, cocaine antinociception was blocked by naloxone (2 mg/kg, IP). The secondary antinociceptive action was also increased by a dose of the kappa-receptor agonist, trans-(+/-)-3,4-di-chloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]-benzene-acetamide methane sulfonate (U-50,488H) (5 mg/kg, IP), which by itself had no antinociceptive effect. Both the initial and secondary antinociceptions were increased following daily cocaine (20 mg/kg, IP) administration for 4 days. 3-(2-Carboxy-piperazin-4-yl) propyl-1-phosphonic acid (CPP) and (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine (MK-801), competitive and noncompetitive NMDA antagonists, respectively, inhibited both the initial and secondary cocaine antinociceptions. Although neither NMDA (5 mg/kg, IP) nor cocaine in lower doses (10 mg/kg, IP) alone produced antinociception, cocaine administered after NMDA produced antinociception. The dopamine D1 receptor agonist 1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepin-7-ol (SK&F38393) enhanced both initial and secondary cocaine antinociceptions, while the D1 receptor antagonist R(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin -7-ol (SCH23390) reversed this potentiating effect. The D2 receptor agonist quinpirole and its antagonist sulpiride exerted opposite effects of their respective D1 counterparts. Both D2 agonist and antagonist were without activity by themselves.(ABSTRACT TRUNCATED AT 250 WORDS)
Ushijima
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I
Department of Neuropsychiatry, Yamaguchi University School of Medicine, Japan.
Horita
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A
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D004357:Drug Synergism; D004723:Endorphins / Q000502:physiology*; D008297:Male; D016202:N-Methylaspartate / Q000502:physiology*; D010147:Pain Measurement / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar
D000700:Analgesics; D015259:Dopamine Agents; D004723:Endorphins; D016202:N-Methylaspartate; D003042:Cocaine; D004298:Dopamine