5-HT2C Agonists Modulate Schizophrenia-Like Behaviors in Mice
Neuropsychopharmacology (2017) 42, 2163–2177 © 2017 American College of Neuropsychopharmacology. All rights reserved 0893-133X/17 www.neuropsychopharmacology.org 5-HT2C Agonists Modulate Schizophrenia-Like Behaviors in Mice 1 1,2 3,7 4 1 Vladimir M Pogorelov , Ramona M Rodriguiz , Jianjun Cheng , Mei Huang , Claire M Schmerberg , 4 5 3 ,1,2,6 Herbert Y Meltzer , Bryan L Roth , Alan P Kozikowski and William C Wetsel* 1 2 Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA; Mouse Behavioral and Neuroendocrine 3 Analysis Core Facility, Duke University Medical Center, Durham, NC, USA; Drug Discovery Program, Department of Medicinal Chemistry and 4 Pharmacognosy, College of Pharmacy, University of Illinois, Chicago, IL, USA; Department of Psychiatry and Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 5National Institute of Mental Health Psychoactive Drug Screening Program, Department of Pharmacology and Division of Chemical Biology and Medicinal Chemistry, University of North Carolina Chapel Hill Medical School, Chapel Hill, NC, 6 USA; Departments of Cell Biology and Neurobiology, Duke University Medical Center, Durham, NC, USA All FDA-approved antipsychotic drugs (APDs) target primarily dopamine D2 or serotonin (5-HT2A) receptors, or both; however, these medications are not universally effective, they may produce undesirable side effects, and provide only partial amelioration of negative and cognitive symptoms. The heterogeneity of pharmacological responses in schizophrenic patients suggests that additional drug targets may be effective in improving aspects of this syndrome. Recent evidence suggests that 5-HT receptors may be a promising target for 2C schizophrenia since their activation reduces mesolimbic nigrostriatal dopamine release (which conveys antipsychotic action), they are expressed almost exclusively in CNS, and have weight-loss-promoting capabilities.
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