title: Interactions of cocaine with morphine, U-50,488H and [D-Pen2, D-Pen5]enkaphalin.
abstract: The effects of acute and chronic administration of cocaine on the antinociception and tolerance to the antinociceptive actions of mu-(morphine), kappa-(U-50,488H), and delta-([D-Pen2,D-Pen5]enkephalin; DPDPE), opioid receptor agonists were determined in male Swiss-Webster mice. Intraperitoneal injection of 40 mg/kg of cocaine by itself produced weak antinociceptive response as measured by the tail-fick test but the lower doses were ineffective. Administration of morphine (10 mg/kg, SC), U-50,488H (25 mg/kg, IP) or DPDPE (10 microg/mouse, ICV) produced antinociception in mice. Cocaine (20 mg/kg) potentiated the antinociceptive action of morphine and DPDPE but had no effect on U-50,488H-induced antinociception. Administration of morphine (20 mg/kg, SC), U-50,488H (25 mg/kg, IP) or DPDPE (20 microg/mouse, ICV) twice a day for 4 days resulted in the development of tolerance to their antinociceptive actions. Tolerance to the antinociceptive actions of morphine and U-50,488H was inhibited by concurrent treatment with 20 or 40 mg/kg doses of cocaine; however, tolerance to the antinociceptive action of DPDPE was not modified by cocaine. It is concluded that cocaine selectively potentiates the antinociceptive action of mu- and delta- but not of the kappa-opioid receptor agonist. On the other hand, cocaine inhibits the development of tolerance to the antinociceptive actions of mu- and kappa- but not of delta-opioid receptor agonists in mice.
authors.affiliation: Department of Pharmaceutics and Pharmacodynamics, The University of Illinois at Chicago, Health Sciences Center, 60612, USA. DRHNB@UIC.EDU
authors.forename: H N
authors.initials: HN
authors.lastname: Bhargava
authors.forename: Y J
authors.initials: YJ
authors.lastname: Cao
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage*; D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D004347:Drug Interactions; D004361:Drug Tolerance; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000008:administration & dosage*; D006358:Hot Temperature; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000502:physiology
chemical_list: D000700:Analgesics; D004745:Enkephalins; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D003042:Cocaine