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Cannabinoid-induced lower lip retraction in rats
Girish R Chopda1,2, Spyros P Nikas1, Rishi Sharma1,3
1Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA.
Psychopharmacology
|November 22, 2018
Summary
Cannabinoid agonists, like Δ9-THC, cause lower lip retraction (LLR) in rats through CB1 receptors. Combining cannabinoid and 5-HT1A agonists results in a synergistic LLR effect.
Area of Science:
- Neuropharmacology
- Behavioral Neuroscience
Background:
- Lower lip retraction (LLR) in rats is a known effect of 5-HT1A agonists.
- LLR was observed with several cannabinoid agonists during behavioral evaluations.
Purpose of the Study:
- To pharmacologically characterize cannabinoid-induced lower lip retraction in rats.
- Investigate the receptor mechanisms underlying cannabinoid-mediated LLR.
Main Methods:
- Administered cannabinoid agonists (Δ9-THC, AM7499, AM2389) and 5-HT1A agonist (8-OH-DPAT) to rats, scoring LLR.
- Utilized antagonists (rimonabant, WAY100635) to assess receptor involvement.
- Examined interactions between cannabinoid and 5-HT1A agonists via pretreatment studies.
Main Results:
- All tested cannabinoid agonists induced LLR.
- AM2389-induced LLR was reduced by rimonabant and WAY100635.
- 8-OH-DPAT-induced LLR was antagonized by WAY100635 but not rimonabant.
- Cannabinoid agonists shifted the 8-OH-DPAT dose-effect curve leftward, indicating supraadditive interactions.
Conclusions:
- Cannabinoid agonists induce LLR in rats via CB1 receptor activation.
- This effect was previously attributed solely to 5-HT1A receptor activity.
- Co-administration of cannabinoid and 5-HT1A agonists produces synergistic LLR.
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