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Modulation of cannabinoid-induced antinociception after intracerebroventricular versus intrathecal administration to mice: possible mechanisms for interaction with morphine.
J Pharmacol Exp Ther. 1995 Jan; 272(1):310-21.JP

Abstract

Dose-effect curves were generated for the cannabinoids [intracerebroventricularly (icv.)] and compared with those previously generated after administration intrathecally (i.t.). The ED50 values after administration of levonantradol, CP 55,940, delta 9-THC and delta 8-THC i.t. vs. icv. did not differ significantly. CP 56,667 was significantly more potent after icv. administration than i.t. administration, and was nearly 10 times more potent than CP 55,940 (icv.). CP 55,940 and CP 56,667, which did not produce greater than additive effects in combination with morphine when the drugs were administered i.t., shifted the morphine (icv.) dose-effect curve in a parallel manner nearly 10-fold after icv. administration. The antinociceptive effects of the cannabinoids (icv.) were not blocked by ICI 174,864 (20 micrograms/mouse), nor-BNI (70 micrograms/mouse) or naloxone (20 micrograms/mouse or 10 mg/kg s.c.). Pertussis toxin pretreatment i.t. for 7 days totally abolished the antinociception produced by the cannabinoids (icv. and i.t.). Pretreatment of the mice with forskolin (i.t.) or Cl-cAMP (10 micrograms/mouse i.t.), which produced no antinociception, significantly attenuated the antinociception produced by the delta 9-THC and CP 55,940. However, when administered icv., forskolin and Cl-cAMP produced antinociception, but did not block or produce greater than additive effects with the antinociception produced by the cannabinoids administered icv. The i.t. administration of calcium and calcium modulators failed to alter the antinociception produced by the i.t. administration of the cannabinoids. Conversely, calcium (icv.) blocked the antinociceptive effects of the cannabinoids. The AD50 values (+/- CL) for calcium-induced block of delta 9-THC, delta 8-THC and CP 55,940 were 215 (94-489), 176 (122-253) and 123 (81-186) nmol/mouse, respectively. omega-Conotoxin (1 micrograms/mouse icv.), which did not alter the antinociceptive effects of delta 9-THC, significantly reversed the calcium-induced blockade of delta 9-THC. Thapsigargin (icv.) blocked the antinociception produced by delta 9-THC and CP 55,940. Apamin, blocker calcium-gated potassium channels, produced a parallel rightward shift in the dose-effect curves of delta 9-THC, delta 8-THC and CP 55,940 (i.t.). However, apamin (5 ng/mouse icv.) failed to block icv. administered cannabinoids. Because acute administration of opiates/opioids have been shown to interact with Gi/o protein-coupled receptors, decrease calcium entry to and content of neurons, reduce cAMP levels and produce hyperpolarization of neurons via both ATP- and apamin-sensitive potassium channels, these three intracellular systems may be common points of interaction with the cannabinoids.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Medical College, Virginia/Virginia Commonwealth University, Richmond.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7815346

Citation

Welch, S P., et al. "Modulation of Cannabinoid-induced Antinociception After Intracerebroventricular Versus Intrathecal Administration to Mice: Possible Mechanisms for Interaction With Morphine." The Journal of Pharmacology and Experimental Therapeutics, vol. 272, no. 1, 1995, pp. 310-21.
Welch SP, Thomas C, Patrick GS. Modulation of cannabinoid-induced antinociception after intracerebroventricular versus intrathecal administration to mice: possible mechanisms for interaction with morphine. J Pharmacol Exp Ther. 1995;272(1):310-21.
Welch, S. P., Thomas, C., & Patrick, G. S. (1995). Modulation of cannabinoid-induced antinociception after intracerebroventricular versus intrathecal administration to mice: possible mechanisms for interaction with morphine. The Journal of Pharmacology and Experimental Therapeutics, 272(1), 310-21.
Welch SP, Thomas C, Patrick GS. Modulation of Cannabinoid-induced Antinociception After Intracerebroventricular Versus Intrathecal Administration to Mice: Possible Mechanisms for Interaction With Morphine. J Pharmacol Exp Ther. 1995;272(1):310-21. PubMed PMID: 7815346.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of cannabinoid-induced antinociception after intracerebroventricular versus intrathecal administration to mice: possible mechanisms for interaction with morphine. AU - Welch,S P, AU - Thomas,C, AU - Patrick,G S, PY - 1995/1/1/pubmed PY - 1995/1/1/medline PY - 1995/1/1/entrez SP - 310 EP - 21 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 272 IS - 1 N2 - Dose-effect curves were generated for the cannabinoids [intracerebroventricularly (icv.)] and compared with those previously generated after administration intrathecally (i.t.). The ED50 values after administration of levonantradol, CP 55,940, delta 9-THC and delta 8-THC i.t. vs. icv. did not differ significantly. CP 56,667 was significantly more potent after icv. administration than i.t. administration, and was nearly 10 times more potent than CP 55,940 (icv.). CP 55,940 and CP 56,667, which did not produce greater than additive effects in combination with morphine when the drugs were administered i.t., shifted the morphine (icv.) dose-effect curve in a parallel manner nearly 10-fold after icv. administration. The antinociceptive effects of the cannabinoids (icv.) were not blocked by ICI 174,864 (20 micrograms/mouse), nor-BNI (70 micrograms/mouse) or naloxone (20 micrograms/mouse or 10 mg/kg s.c.). Pertussis toxin pretreatment i.t. for 7 days totally abolished the antinociception produced by the cannabinoids (icv. and i.t.). Pretreatment of the mice with forskolin (i.t.) or Cl-cAMP (10 micrograms/mouse i.t.), which produced no antinociception, significantly attenuated the antinociception produced by the delta 9-THC and CP 55,940. However, when administered icv., forskolin and Cl-cAMP produced antinociception, but did not block or produce greater than additive effects with the antinociception produced by the cannabinoids administered icv. The i.t. administration of calcium and calcium modulators failed to alter the antinociception produced by the i.t. administration of the cannabinoids. Conversely, calcium (icv.) blocked the antinociceptive effects of the cannabinoids. The AD50 values (+/- CL) for calcium-induced block of delta 9-THC, delta 8-THC and CP 55,940 were 215 (94-489), 176 (122-253) and 123 (81-186) nmol/mouse, respectively. omega-Conotoxin (1 micrograms/mouse icv.), which did not alter the antinociceptive effects of delta 9-THC, significantly reversed the calcium-induced blockade of delta 9-THC. Thapsigargin (icv.) blocked the antinociception produced by delta 9-THC and CP 55,940. Apamin, blocker calcium-gated potassium channels, produced a parallel rightward shift in the dose-effect curves of delta 9-THC, delta 8-THC and CP 55,940 (i.t.). However, apamin (5 ng/mouse icv.) failed to block icv. administered cannabinoids. Because acute administration of opiates/opioids have been shown to interact with Gi/o protein-coupled receptors, decrease calcium entry to and content of neurons, reduce cAMP levels and produce hyperpolarization of neurons via both ATP- and apamin-sensitive potassium channels, these three intracellular systems may be common points of interaction with the cannabinoids. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/7815346/Modulation_of_cannabinoid_induced_antinociception_after_intracerebroventricular_versus_intrathecal_administration_to_mice:_possible_mechanisms_for_interaction_with_morphine_ DB - PRIME DP - Unbound Medicine ER -