Reversal of SR 141716A-induced head-twitch and ear-scratch responses in mice by Δ9,-THC and other cannabinoids

Document Type

Article

Publication Title

Pharmacology Biochemistry and Behavior

Abstract

Recently, we have shown that cannabinoids of diverse structure block the ability of the selective 5-HT2A/C agonist DOI to produce the head-twitch response (HTR) and the ear-scratch response (ESR) in mice. The cannabinoid CB1 antagonist/inverse agonist SR 141716A also induces these behaviors in mice. The purposes of the present study were: (1) to investigate whether Δ9-tetrahydrocannabinol (Δ9-THC) and other cannabinoids HU-210 and WIN 55, 212-2 can prevent SR 141716A-induced HTR and ESR and (2) to evaluate any correlation between the ID50 potency order of the cited cannabinoids in blocking SR 141716A-induced HTR and ESR and their ED50 order of potency in reducing spontaneous locomotor activity and rearing behavior. For the SR 141716A reversal study, different groups of mice were injected intraperitoneally with either vehicle or varying doses of the following cannabinoids: Δ9-THC (2.5-20 mg/kg), Δ8-THC (5-20 mg/kg), HU-210 (0.05-0.5 mg/kg), CP 55, 940 (0.5-2.5 mg/kg) and WIN 55, 212-2 (2.5-10 mg/kg). Thirty minutes later, each mouse received SR 141716A (2.5 mg/kg ip) and the frequencies of the induced behaviors (mean ± S.E.M.) were recorded for the next 30 min. The effects of the cited doses of cannabinoids were also examined on spontaneous locomotor activity and rearing frequency for a 20-min duration 10 min after cannabinoid injection. The tested cannabinoids reduced the frequencies of HTR and ESR in SR 141716A-injected mice. These agents also attenuated the cited naturally occurring repertoire of motor parameters in mice. Although large potency differences were observed among the cited cannabinoids, each tested cannabinoid was relatively equipotent in preventing locomotor parameters and SR 141716A-induced behaviors. The ID50 potency order of cannabinoids in blocking SR 141716A-induced HTR and ESR were similar (HU-210 > CP 55, 940 > WIN 55, 212-2 ≥ Δ9-THC = Δ8-THC), and are comparable with: (1) their ED50 potency order in attenuating both spontaneous locomotor activity and rearing behavior (HU-210 > CP 55, 940 > WIN 55, 212-2 > Δ9-THC = Δ8-THC) and (2) their published ED50 potency order for producing the tetrad of behaviors in mice as well as their rank order of binding affinities for cannabinoid CB1 receptors. The present data show that cannabinoids of diverse structure prevent SR 141716A-induced HTR and ESR, and inhibition of these behaviors by cannabinoids could be used as a new index of cannabimimetic activity. © 2002 Elsevier Science Inc. All rights reserved.

First Page

155

Last Page

162

DOI

10.1016/S0091-3057(01)00647-5

Publication Date

1-2-2002

This document is currently not available here.

Share

COinS