title: HSV-Mediated Transgene Expression of Chimeric Constructs to Study Behavioral Function of GPCR Heteromers in Mice.
abstract: The heteromeric receptor complex between 5-HT2A and mGlu2 has been implicated in some of the behavioral phenotypes in mouse models of psychosis(1,2). Consequently, investigation of structural details of the interaction between 5-HT2A and mGlu2 affecting schizophrenia-related behaviors represents a powerful translational tool. As previously shown, the head-twitch response (HTR) in mice is elicited by hallucinogenic drugs and this behavioral response is absent in 5-HT2A knockout (KO) mice(3,4). Additionally, by conditionally expressing the 5-HT2A receptor only in cortex, it was demonstrated that 5-HT2A receptor-dependent signaling pathways on cortical pyramidal neurons are sufficient to elicit head-twitch behavior in response to hallucinogenic drugs(3). Finally, it has been shown that the head-twitch behavioral response induced by the hallucinogens DOI and lysergic acid diethylamide (LSD) is significantly decreased in mGlu2-KO mice(5). These findings suggest that mGlu2 is at least in part necessary for the 5-HT2A receptor-dependent psychosis-like behavioral effects induced by LSD-like drugs. However, this does not provide evidence as to whether the 5-HT2A-mGlu2 receptor complex is necessary for this behavioral phenotype. To address this question, herpes simplex virus (HSV) constructs to express either mGlu2 or mGlu2ΔTM4N (mGlu2/mGlu3 chimeric construct that does not form the 5-HT2A-mGlu2 receptor complex) in the frontal cortex of mGlu2-KO mice were used to examine whether this GPCR heteromeric complex is needed for the behavioral effects induced by LSD-like drugs(6).
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai.
authors: Terrell
authors: T
authors: Holloway
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai.
authors: Jose L
authors: JL
authors: Moreno
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai; Department of Neurology, Icahn School of Medicine at Mount Sinai; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai; Department of Physiology and Biophysics, Virginia Commonwealth University Medical School; javier.gonzalez-maeso@vcuhealth.org.
authors: Javier
authors: J
authors: González-Maeso
mesh_terms: D000818:Animals; D006213:Hallucinogens; D008238:Lysergic Acid Diethylamide; D051379:Mice; D018345:Mice, Knockout; D044402:Receptor, Serotonin, 5-HT2A; D018139:Simplexvirus; D019076:Transgenes
chemical_list: D006213:Hallucinogens; D044402:Receptor, Serotonin, 5-HT2A; D008238:Lysergic Acid Diethylamide