Effects of acute treatments with the serotonin 2A antagonist M100907 alone or in combination with the serotonin 2C agonist WAY163909 on methamphetamine self-administration in rhesus monkeys

Autor(es)

Odabas-Geldiay, Melis ^[1] ; Shields, Hannah ^[1] ; Berro, Lais F. ^{[1, 2]} ; Rice, Kenner C. ^[3] ; Howell, Leonard L. ^{[1, 4]}

Afiliação do(s) autor(es)

^[1] Emory Univ, Yerkes Natl Primate Res Ctr, 954 Gatewood Rd NE, Atlanta, GA 30329 - USA

^[2] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, 2500 N State St, Jackson, MS 39216 - USA

^[3] NIDA, Drug Design & Synth Sect, Mol Targets & Medicat Discovery Branch, Rockville, MD - USA

^[4] Emory Univ, Emory Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 - USA

• Tipo de documento: Artigo Científico
• Fonte: DRUG AND ALCOHOL DEPENDENCE; v. 194, p. 252-256, JAN 1 2019.
• Citações Web of Science: 0

Resumo

Background: Serotonin 5-HT2A receptor antagonists and 5-HT2C receptor agonists have been proposed as important candidates for the development of pharmacotherapies for psychostimulant abuse, with evidence suggesting that those receptors may act together to control behavior. However, the role of 5-HT2A receptors on the reinforcing effects of psychostimulant drugs has not been fully elucidated. Methods: In the present study, we investigated the effects of the selective 5HT(2A) receptor antagonist M100907 alone or in combination with the selective 5HT(2C) agonist WAY 163909 on intravenous methamphetamine self administration in rhesus macaques (N = 3). Methamphetamine self-administration (0.01-0.03 mg/kg/inf) was evaluated under a fixed-ratio 20-schedule of reinforcement, and acute pretreatments were conducted 1 h (M100907) or 45 min (WAY 163,909) prior to the beginning of self-administration sessions at the EDMax dose of methamphetamine once stability criteria were met. Results: Pretreatment with M100907 (0.03-0.3 mg/kg, i.m.) dose-dependently attenuated methamphetamine self-administration, with the highest dose significantly decreasing response rates compared to vehicle. Combined administration of ineffective doses of M100907 and WAY 163,909 had no effects on methamphetamine self administration. Conclusions: Our study indicates that acute selective 5-HT2A receptor blockade decreases peak methamphetamine intake in nonhuman primates. Combination approaches with sub-threshold doses of 5-HT2A receptor antagonists and 5-HT2C receptor agonists, on the other hand, do not seem to be effective in decreasing methamphetamine reinforcement. Further studies are needed in order to investigate the effects of chronic treatments with M100 on complete METH SA dose-response curves. (AU)

• Processo FAPESP: 15/25482-3 - Efeitos de drogas hipnóticas em comportamentos relacionados ao uso de metanfetamina: um estudo etológico e molecular em roedores e primatas não-humanos
• Beneficiário: Laís Fernanda Berro
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado