Cannabinoids of diverse structure inhibit two DOI-induced 5-HT2A receptor-mediated behaviors in mice

Document Type

Article

Publication Title

Pharmacology Biochemistry and Behavior

Abstract

We have recently shown that the selective cannabinoid CB1 receptor antagonist SR 141716A produces robust frequencies of head-twitch response (HTR) and ear-scratch response (ESR) in drug-naive mice. Both behaviors were potently blocked by the selective 5-HT2A/C receptor antagonist SR 46349B. Selective 5-HT2A/C agonists such as DOI also produce these behaviors in mice. The purpose of the present study was to: (1) investigate whether Δ9-tetrahydrocannabinol (Δ9-THC) and its analogs [Δ8-tetrahydrocannabinol (Δ8-THC), HU-210, CP 55,940, and WIN 55,212-2] can prevent the DOI-induced behaviors and (2) to see whether any correlation exists in the ID50 potency order of these cannabinoids in inhibiting the DOI-induced HTR and ESR relative to their published ED50 potency profiles in producing the tetrad of behaviors in mice. Thus, at 0 min, different groups of mice were injected intraperitoneally with either vehicle or varying doses of the following cannabinoids: Δ9-THC (0.25-20 mg/kg), Δ8-THC (2.5-20 mg/kg), HU-210 (0.02-0.5 mg/kg), CP 55,940 (0.004-0.5 mg/kg), and WIN 55,212-2 (0.5-10 mg/kg). Twenty minutes later, each mouse received an intraperitoneal injection of DOI (1 mg/kg) and the frequencies of DOI-induced behaviors (mean ± S.E.M.) were recorded for the next 20 min. The tested cannabinoids reduced the frequencies of both DOI-induced HTR and ESR in a dose-dependent fashion. HU-210 was the most potent inhibitor of HTR, whereas CP 55,940 was most effective against ESR. The ID50 potency order of cannabinoids in blocking the HTR is: HU-210 > CP 55,940 > WIN 55,212-2 > Δ9-THC > Δ8-THC, which is identical to their published order of potency in producing the tetrad of behaviors in mice. On the other hand, they had the following ID50 potency order against the ESR: CP 55,940 > HU-210 > WIN 55,212-2 > Δ9-THC > Δ8-THC. The tested cannabinoids were 3-30 times more potent in preventing the ESR than the HTR. The data show that cannabinoids inhibit 5-HT2A receptor-mediated functions in a potent but differential manner. © 2001 Elsevier Science Inc.

First Page

311

Last Page

317

DOI

10.1016/S0091-3057(00)00477-9

Publication Date

4-2-2001

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