The effect of Δ9-tetrahydrocannabinol on 5-HT3 receptors depends on the current density.
K H S Yang, D Isaev, M Morales, G Petroianu, S Galadari, M Oz
Neuroscience November 24, 2010 DOI: 10.1016/j.neuroscience.2010.08.044 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro electrophysiology and radioligand binding study Peer reviewed |
|---|---|
| Population | Xenopus oocytes expressing 5-HT3A receptors and adult rat nodose ganglion neurons |
| Intervention | THC |
| Dose | 1 µM |
| Topics | Cannabis Serotonin |
| Key points | THC inhibited 5-HT3 receptor-mediated currents in a concentration-dependent, noncompetitive manner in both oocytes and rat neurons, with inhibition inversely related to receptor density. The authors propose this inhibition may contribute to THC's pharmacological actions in nociception and emesis. |
Abstract
The effects of Δ(9)-tetrahydrocannabinol (THC), the psychoactive component of cannabis, on the function of 5-HT type 3 (5-HT(3)) receptors were investigated using a two-electrode voltage clamp technique in Xenopus oocytes, and a whole-cell patch clamp technique in rat nodose ganglion neurons. In oocytes injected with 3 ng cRNA of 5-HT(3A) receptor, THC reversibly inhibited currents evoked with 5-HT (1 μM) in a concentration-dependent manner (IC(50)=1.2 μM). The extent of THC inhibition was inversely correlated with the amount of cRNA injected and the mean 5-HT(3A) receptor current densities. Pretreatment with actinomycin D, which inhibits transcription, decreased the mean 5-HT(3) receptor current density and increased the extent of THC inhibition on 5-HT(3) receptor-mediated currents. The IC(50) values for THC increased from 285 nM to 1.2 μM in oocytes injected with 1 and 3 ng of 5-HT(3A) cRNA, respectively. In radioligand binding studies on membrane preparations of oocytes expressing 5-HT(3A) receptors, THC did not alter the specific binding of a 5-HT(3A) receptor antagonist, [(3)H]GR65630. In the presence of 1 μM THC, the maximum 5-HT-induced response was also inhibited without a significant change in 5-HT potency, indicating that THC acts as a noncompetitive antagonist on 5-HT(3) receptors. In adult rat nodose ganglion neurons, application of 1 μM THC caused a significant inhibition of 5-HT(3) receptors, extent of which correlated with the density of 5-HT-induced currents, indicating that the observed THC effects occur in mammalian neurons. The inhibition of 5-HT(3) receptors by THC may contribute to its pharmacological actions in nociception and emesis.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.