Intracerebroventricular administration of kappa-agonists induces convulsions in mice

Brain Res Bull. 1991 Jul;27(1):75-9. doi: 10.1016/0361-9230(91)90283-p.

Abstract

Intracerebroventricular (ICV) administration of kappa-agonists (PD 117302, U-50488H and U-69593) induced convulsions in a dose-related manner in mice. The dose at which 50% of animals convulsed (CD50) was in nmol ranges for all opioids. Among the opioids used, PD 117302 was the most potent convulsant. ICV administration of either vehicle alone or U-53445E, a non-kappa-opioid (+) enantiomer of U-50488H did not induce convulsions. The convulsive response of kappa-agonists was differentially susceptible for antagonism by naloxone and/or MR 2266. Collectively, these findings support the view that convulsions induced by kappa-agonists in mice involve stereospecific opioid receptor mechanisms. Furthermore, the convulsant effect of kappa-agonists could not be modified by pretreatment with MK-801, ketamine, muscimol or baclofen. It is concluded that kappa-opioid but not NMDA or GABA receptor mechanisms are involved in convulsions induced by kappa-agonists. These results are the first experimental evidence implicating stereospecific kappa-receptor mechanisms in opioid-induced convulsions in mice.

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Analgesics / pharmacology*
  • Animals
  • Baclofen / pharmacology
  • Benzeneacetamides*
  • Benzomorphans / pharmacology
  • Cerebral Ventricles / drug effects
  • Cerebral Ventricles / physiology*
  • Cerebral Ventricles / physiopathology
  • Convulsants / pharmacology
  • Dizocilpine Maleate / pharmacology
  • Injections, Intraventricular
  • Ketamine / pharmacology
  • Mice
  • Mice, Inbred Strains
  • Muscimol / pharmacology
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology*
  • Narcotics / pharmacology*
  • Pyrroles / pharmacology
  • Pyrrolidines / pharmacology
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / physiology*
  • Receptors, Opioid, kappa
  • Seizures / chemically induced
  • Seizures / physiopathology*
  • Stereoisomerism
  • Thiophenes / pharmacology

Substances

  • Analgesics
  • Benzeneacetamides
  • Benzomorphans
  • Convulsants
  • Narcotic Antagonists
  • Narcotics
  • Pyrroles
  • Pyrrolidines
  • Receptors, Opioid
  • Receptors, Opioid, kappa
  • Thiophenes
  • PD 117302
  • Muscimol
  • Naloxone
  • MR 2266
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Ketamine
  • Dizocilpine Maleate
  • Baclofen
  • U 69593