title: 5-HT2A/C receptors mediate the antipsychotic-like effects of alstonine.
abstract: The purpose of this study was to determine the effects of alstonine, an indole alkaloid with putative antipsychotic effects, on working memory by using the step-down inhibitory avoidance paradigm and MK801-induced working memory deficits in mice. Additionally, the role of serotonin 5-HT2A/C receptors in the effects of alstonine on mouse models associated with positive (MK801-induced hyperlocomotion), negative (MK801-induced social interaction deficit), and cognitive (MK801-induced working memory deficit) schizophrenia symptoms was examined. Treatment with alstonine was able to prevent MK801-induced working memory deficit, indicating its potential benefit for cognitive deficits now seen as a core symptom in the disease. Corroborating previously reported data, alstonine was also effective in counteracting MK801-induced hyperlocomotion and social interaction deficit. Ritanserin, a 5-HT2A/C receptor antagonist, prevented alstonine's effects on these three behavioral parameters. This study presents additional evidence that 5-HT2A/C receptors are central to the antipsychotic-like effects of alstonine, consistently seen in mouse models relevant to the three dimensions of schizophrenia symptoms.
authors.affiliation: Laboratório de Etnofarmacologia, Depto de Farmacologia, ICBS, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite 500/202, 90050-170, Porto Alegre, RS, Brazil. vivilinck@gmail.com
authors.forename: V M
authors.initials: VM
authors.lastname: Linck
authors.forename: M M
authors.initials: MM
authors.lastname: Bessa
authors.forename: A P
authors.initials: AP
authors.lastname: Herrmann
authors.forename: M M
authors.initials: MM
authors.lastname: Iwu
authors.forename: C O
authors.initials: CO
authors.lastname: Okunji
authors.forename: E
authors.initials: E
authors.lastname: Elisabetsky
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016291:Dizocilpine Maleate / Q000633:toxicity; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D046948:Secologanin Tryptamine Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D046948:Secologanin Tryptamine Alkaloids; D016291:Dizocilpine Maleate; C009244:serpentine (alkaloid)