Rationale: Lower lip retraction (LLR) in rats has been described as a distinctive effect of 5-HT agonists. In the course of evaluating behavioral effects of cannabinoid agonists in rats, LLR effects were evident following injection of several cannabinoid agonists.
Objectives: To pharmacologically characterize cannabinoid-induced LLR in rats.
Methods: Lower lip retraction was scored using a 3-point scale for up to 6 h after injection of the cannabinoid agonists Δ-tetrahydrocannabinol (Δ-THC, 1-10 mg/kg), AM7499 (0.01-1.0 mg/kg), or AM2389 (0.003-0.1 mg/kg), or, for comparison, the 5-HT agonist 8-OH-DPAT (0.01-0.3 mg/kg). Next, antagonist effects of rimonabant (1-10 mg/kg) and WAY100635 (0.3 mg/kg) on LLR produced by cannabinoid or 5-HT agonists were evaluated. Lastly, effects of 8-OH-DPAT were determined following pretreatment with AM2389 (0.003-0.01 mg/kg) or Δ-THC (1 mg/kg).
Results: All three cannabinoid agonists produced LLR. Effects of AM2389 were attenuated by both rimonabant and WAY100635 whereas effects of 8-OH-DPAT were antagonized by WAY 100635 but not by rimonabant. Pretreatment with 1 mg/kg Δ-THC or 0.01 mg/kg AM2389 shifted the 8-OH-DPAT dose-effect function for LLR to the left and isobolographic analysis of the data indicates CB1 and 5-HT interactions can be supraadditive.
Conclusions: Cannabinoid agonists produce LLR in rats, an effect heretofore ascribed only to activity at 5-HT receptors, via CB1 receptor-mediated actions. Co-administration of a cannabinoid agonist and the 5-HT agonist 8-OH-DPAT results in a synergistic effect on LLR.
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| http://dx.doi.org/10.1007/s00213-018-5125-z | DOI Listing |
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