Tags

Type your tag names separated by a space and hit enter

Sex differences in cannabinoid 1 vs. cannabinoid 2 receptor-selective antagonism of antinociception produced by delta9-tetrahydrocannabinol and CP55,940 in the rat.
J Pharmacol Exp Ther. 2012 Mar; 340(3):787-800.JP

Abstract

The purpose of this study was to determine whether sex differences in cannabinoid (CB)-induced antinociception and motoric effects can be attributed to differential activation of CB(1) or CB(2) receptors. Rats were injected intraperitoneally with vehicle, rimonabant [5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide (SR141716A), a putative CB(1) receptor-selective antagonist; 0.1-10 mg/kg] or 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide (SR144528) (a putative CB(2) receptor-selective antagonist; 1.0-10 mg/kg). Thirty minutes later, Δ(9)-tetrahydrocannabinol (THC; 1.25-40 mg/kg) or 5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]phenol (CP55,940) (0.05-1.6 mg/kg) was injected. Paw pressure and tail withdrawal antinociception, locomotor activity, and catalepsy were measured. Rimonabant dose-dependently antagonized THC and CP55,940 in each test, but was up to 10 times more potent in female than male rats on the nociceptive tests; estimates of rimonabant affinity (apparent pK(B)) for the CB(1) receptor were approximately 0.5 to 1 mol/kg higher in female than male rats. SR144528 partially antagonized THC-induced tail withdrawal antinociception and locomotor activity in females, but this antagonism was not dose-dependent or consistent; no SR144528 antagonism was observed in either sex tested with CP55,940. Neither the time course of rimonabant antagonism nor the plasma levels of rimonabant differed between the sexes. Rimonabant and SR144528 did not antagonize morphine-induced antinociception, and naloxone did not antagonize THC-induced antinociception in either sex. These results suggest that THC produces acute antinociceptive and motoric effects via activation of CB(1), and perhaps under some conditions, CB(2) receptors, in female rats, whereas THC acts primarily at CB(1) receptors in male rats. Higher apparent pK(B) for rimonabant in female rats suggests that cannabinoid drugs bind with greater affinity to CB(1) receptors in female than male rats, probably contributing to greater antinociceptive effects observed in female compared with male rats.

Authors+Show Affiliations

Department of Psychology, Washington State University, Pullman, WA 99164-4820, USA. craft@wsu.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22182934

Citation

Craft, Rebecca M., et al. "Sex Differences in Cannabinoid 1 Vs. Cannabinoid 2 Receptor-selective Antagonism of Antinociception Produced By Delta9-tetrahydrocannabinol and CP55,940 in the Rat." The Journal of Pharmacology and Experimental Therapeutics, vol. 340, no. 3, 2012, pp. 787-800.
Craft RM, Wakley AA, Tsutsui KT, et al. Sex differences in cannabinoid 1 vs. cannabinoid 2 receptor-selective antagonism of antinociception produced by delta9-tetrahydrocannabinol and CP55,940 in the rat. J Pharmacol Exp Ther. 2012;340(3):787-800.
Craft, R. M., Wakley, A. A., Tsutsui, K. T., & Laggart, J. D. (2012). Sex differences in cannabinoid 1 vs. cannabinoid 2 receptor-selective antagonism of antinociception produced by delta9-tetrahydrocannabinol and CP55,940 in the rat. The Journal of Pharmacology and Experimental Therapeutics, 340(3), 787-800. https://doi.org/10.1124/jpet.111.188540
Craft RM, et al. Sex Differences in Cannabinoid 1 Vs. Cannabinoid 2 Receptor-selective Antagonism of Antinociception Produced By Delta9-tetrahydrocannabinol and CP55,940 in the Rat. J Pharmacol Exp Ther. 2012;340(3):787-800. PubMed PMID: 22182934.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sex differences in cannabinoid 1 vs. cannabinoid 2 receptor-selective antagonism of antinociception produced by delta9-tetrahydrocannabinol and CP55,940 in the rat. AU - Craft,Rebecca M, AU - Wakley,Alexa A, AU - Tsutsui,Kimberly T, AU - Laggart,Jillian D, Y1 - 2011/12/19/ PY - 2011/12/21/entrez PY - 2011/12/21/pubmed PY - 2012/5/5/medline SP - 787 EP - 800 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 340 IS - 3 N2 - The purpose of this study was to determine whether sex differences in cannabinoid (CB)-induced antinociception and motoric effects can be attributed to differential activation of CB(1) or CB(2) receptors. Rats were injected intraperitoneally with vehicle, rimonabant [5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide (SR141716A), a putative CB(1) receptor-selective antagonist; 0.1-10 mg/kg] or 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide (SR144528) (a putative CB(2) receptor-selective antagonist; 1.0-10 mg/kg). Thirty minutes later, Δ(9)-tetrahydrocannabinol (THC; 1.25-40 mg/kg) or 5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]phenol (CP55,940) (0.05-1.6 mg/kg) was injected. Paw pressure and tail withdrawal antinociception, locomotor activity, and catalepsy were measured. Rimonabant dose-dependently antagonized THC and CP55,940 in each test, but was up to 10 times more potent in female than male rats on the nociceptive tests; estimates of rimonabant affinity (apparent pK(B)) for the CB(1) receptor were approximately 0.5 to 1 mol/kg higher in female than male rats. SR144528 partially antagonized THC-induced tail withdrawal antinociception and locomotor activity in females, but this antagonism was not dose-dependent or consistent; no SR144528 antagonism was observed in either sex tested with CP55,940. Neither the time course of rimonabant antagonism nor the plasma levels of rimonabant differed between the sexes. Rimonabant and SR144528 did not antagonize morphine-induced antinociception, and naloxone did not antagonize THC-induced antinociception in either sex. These results suggest that THC produces acute antinociceptive and motoric effects via activation of CB(1), and perhaps under some conditions, CB(2) receptors, in female rats, whereas THC acts primarily at CB(1) receptors in male rats. Higher apparent pK(B) for rimonabant in female rats suggests that cannabinoid drugs bind with greater affinity to CB(1) receptors in female than male rats, probably contributing to greater antinociceptive effects observed in female compared with male rats. SN - 1521-0103 UR - https://www.unboundmedicine.com/medline/citation/22182934/Sex_differences_in_cannabinoid_1_vs__cannabinoid_2_receptor_selective_antagonism_of_antinociception_produced_by_delta9_tetrahydrocannabinol_and_CP55940_in_the_rat_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=22182934 DB - PRIME DP - Unbound Medicine ER -