5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens.
Richard A. Rabin, Meredith J. Regina, Mireille M Doat, Jerrold C Winter
Pharmacology, biochemistry, and behavior May 2002 DOI: 10.1016/s0091-3057(01)00720-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory study Peer reviewed |
|---|---|
| Population | PC12 cells stably expressing the rat 5-HT2A receptor |
| Topics | Serotonin |
| Key points | Hallucinogens and some nonhallucinogens stimulated 5-HT2A-mediated phosphoinositide hydrolysis, but efficacy did not correlate with discriminative effects in animals, suggesting this pathway is not the sole critical signaling mechanism for hallucinogen discrimination. |
Abstract
The role of 5-HT2A-mediated stimulation of phosphoinositide hydrolysis in the discriminative effects of hallucinogens was investigated in PC12 cells stably expressing the rat 5-HT2A receptor (PC12-5-HT2A cells). The hallucinogenic compounds, D-lysergic acid diethylamide (LSD), (-)2,5-dimethoxy-4-methylamphetamine (DOM), psilocybin, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (MDMT) and N,N-diethyltryptamine (DET), all caused a concentration-dependent increase in the generation of [3H]inositol phosphates. The nonhallucinogenic compounds, 6-fluoro-N,N-diethyltryptamine (6-F-DET), lisuride and quipazine, also displayed significant efficacy in stimulating phosphoinositide hydrolysis, while 2-bromo-lysergic acid diethylamide (BOL), which is not a hallucinogen, did not alter inositol phosphate generation. The beta-carbolines, harmaline and harmane, also did not alter phosphoinositide hydrolysis. Comparison of these results with previous drug discrimination studies indicated the apparent lack of correlation between the degree of substitution in LSD- and DOM-trained animals and efficacy in stimulating phosphoinositide hydrolysis. The present study indicates that 5-HT2A-mediated stimulation of phosphoinositide hydrolysis does not appear to be the sole critical signaling mechanism involved in the discriminative effects of hallucinogens.