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The role of endogenous opioids in enhancing the antinociception produced by the combination of delta 9-tetrahydrocannabinol and morphine in the spinal cord.
J Pharmacol Exp Ther. 1996 Nov; 279(2):608-16.JP

Abstract

We have shown previously that intrathecal (i.t.) administration of the combination of delta 9-tetrahydrocannabinol (THC) and morphine results in a greater than additive antinociceptive effect. Similarly, pretreating mice with subthreshold doses of the kappa agonist, Dynorphin A (1-8), produced a parallel, leftward shift of the morphine dose-response curve, shifting the ED50 of morphine from 0.32 to 0.04 micrograms/mouse. A cocktail of enzyme inhibitors used to prevent the metabolism of Dynorphin A (1-8) into the delta receptor agonist, [Leu5]-enkephalin, attenuated the enhancement of morphine-induced antinociception by delta 9-THC. The enhanced antinociceptive effect observed after i.t. administration of the combination of delta 9-THC and morphine was also attenuated with antisera to Dynorphin A (1-8) (10 micrograms/ mouse) and Dynorphin A (1-13) (10 micrograms/mouse). Antisera to Dynorphin A (1-8) and Dynorphin A (1-17) blocked the antinociceptive effects of delta 9-THC (50 micrograms i.t.) without producing any significant alteration in the hypothermic and cataleptic effects or hypomotility produced by delta 9-THC. The antinociception produced by the combination of delta 9-THC and morphine was blocked by the kappa antagonist, nor-binaltorphimine (2 micrograms/ mouse), as well as the delta antagonist, naltrindole (5 micrograms/ mouse). Thus, the antinociception of morphine, which is mediated predominately by mu receptors, may be enhanced by delta 9-THC through the activation of kappa and delta receptors.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

8930163

Citation

Pugh, G, et al. "The Role of Endogenous Opioids in Enhancing the Antinociception Produced By the Combination of Delta 9-tetrahydrocannabinol and Morphine in the Spinal Cord." The Journal of Pharmacology and Experimental Therapeutics, vol. 279, no. 2, 1996, pp. 608-16.
Pugh G, Smith PB, Dombrowski DS, et al. The role of endogenous opioids in enhancing the antinociception produced by the combination of delta 9-tetrahydrocannabinol and morphine in the spinal cord. J Pharmacol Exp Ther. 1996;279(2):608-16.
Pugh, G., Smith, P. B., Dombrowski, D. S., & Welch, S. P. (1996). The role of endogenous opioids in enhancing the antinociception produced by the combination of delta 9-tetrahydrocannabinol and morphine in the spinal cord. The Journal of Pharmacology and Experimental Therapeutics, 279(2), 608-16.
Pugh G, et al. The Role of Endogenous Opioids in Enhancing the Antinociception Produced By the Combination of Delta 9-tetrahydrocannabinol and Morphine in the Spinal Cord. J Pharmacol Exp Ther. 1996;279(2):608-16. PubMed PMID: 8930163.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of endogenous opioids in enhancing the antinociception produced by the combination of delta 9-tetrahydrocannabinol and morphine in the spinal cord. AU - Pugh,G,Jr AU - Smith,P B, AU - Dombrowski,D S, AU - Welch,S P, PY - 1996/11/1/pubmed PY - 2001/3/28/medline PY - 1996/11/1/entrez SP - 608 EP - 16 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 279 IS - 2 N2 - We have shown previously that intrathecal (i.t.) administration of the combination of delta 9-tetrahydrocannabinol (THC) and morphine results in a greater than additive antinociceptive effect. Similarly, pretreating mice with subthreshold doses of the kappa agonist, Dynorphin A (1-8), produced a parallel, leftward shift of the morphine dose-response curve, shifting the ED50 of morphine from 0.32 to 0.04 micrograms/mouse. A cocktail of enzyme inhibitors used to prevent the metabolism of Dynorphin A (1-8) into the delta receptor agonist, [Leu5]-enkephalin, attenuated the enhancement of morphine-induced antinociception by delta 9-THC. The enhanced antinociceptive effect observed after i.t. administration of the combination of delta 9-THC and morphine was also attenuated with antisera to Dynorphin A (1-8) (10 micrograms/ mouse) and Dynorphin A (1-13) (10 micrograms/mouse). Antisera to Dynorphin A (1-8) and Dynorphin A (1-17) blocked the antinociceptive effects of delta 9-THC (50 micrograms i.t.) without producing any significant alteration in the hypothermic and cataleptic effects or hypomotility produced by delta 9-THC. The antinociception produced by the combination of delta 9-THC and morphine was blocked by the kappa antagonist, nor-binaltorphimine (2 micrograms/ mouse), as well as the delta antagonist, naltrindole (5 micrograms/ mouse). Thus, the antinociception of morphine, which is mediated predominately by mu receptors, may be enhanced by delta 9-THC through the activation of kappa and delta receptors. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8930163/The_role_of_endogenous_opioids_in_enhancing_the_antinociception_produced_by_the_combination_of_delta_9_tetrahydrocannabinol_and_morphine_in_the_spinal_cord_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8930163 DB - PRIME DP - Unbound Medicine ER -