5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens

Pharmacology, Biochemistry, and Behavior
Richard A RabinJ C Winter

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 hydroly...Continue Reading

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Citations

Nov 26, 2009·Psychopharmacology·Adam L Halberstadt, Mark A Geyer
Feb 6, 2004·Pharmacology & Therapeutics·David E Nichols
Feb 5, 2016·Pharmacological Reviews·David E Nichols
Mar 23, 2005·Medical Hypotheses·Michael S Jacob, David E Presti
Nov 6, 2007·Biochemical Pharmacology·William E FantegrossiChad J Reissig
Jul 19, 2014·Behavioural Brain Research·Adam L Halberstadt
Mar 1, 2018·British Journal of Pharmacology·I AntoniadouT Sharp
Jun 29, 2006·The Journal of Pharmacology and Experimental Therapeutics·Jonathan D UrbanRichard B Mailman
Sep 14, 2018·Frontiers in Behavioral Neuroscience·Bruno Lobao-SoaresAna Carolina Luchiari
Nov 20, 2021·Journal of Neurochemistry·Samuel T SlocumBryan L Roth

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