Investigação dos mecanismos envolvidos nos efeitos comportamentais da metanfetamina relacionados ao sono e à dependência química em macacos rhesus

• Ano de defesa: 2017
• Autor(a) principal: Berro, Laís Fernanda [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Methamphetamine; Sleep; Self-Administration; Actigraphy; Microdialysis; Rhesus Monkeys; Metanfetamina; Sono; Autoadministração; Actigrafia; Microdiálise; Macacos rhesus; Macaca mulatta
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5072928; http://repositorio.unifesp.br/handle/11600/50408

Sleep disorders and substance abuse are highly comorbid. The GABAergic and serotonergic systems participate in the regulation of both drug addiction and sleep-wake cycle. The aim of the present study was to evaluate the mechanisms underlying the abuse- and sleep-related behavioral effects of methamphetamine (METH) in rhesus monkeys. Our results show that METH disrupts sleep on the first day of self-administration, and that in the absence of the drug and of drug-associated cues (extinction), the sleep condition is restored to baseline levels. The reintroduction of drug-conditioned cues during effective reinstatement sessions induced sleep disruption. Tolerance can develop to the sleep-disrupting and locomotor stimulant effects of METH if self-administration sessions exceed 5 consecutive days, effect that is attenuated by the inclusion of washout periods between self-administration blocks. Treatment with the GABAA receptor modulator temazepam at a high dose attenuated METH self-administration and METH-induced dopamine overflow in the nucleus accumbens (NAc). The GABAA receptor modulator eszopiclone exerted did not alter METH effects. Moreover, treatments based on GABAA receptor modulators were not effective in improving sleep measures disrupted by METH. Night treatment with the selective 5-HT2C receptor agonist WAY163909, on the other hand, was effective in attenuating the effects of METH on sleep. WAY163909 also attenuated METH intake, METH-induced reinstatement and METH-induced dopamine overflow in the NAc. Extending those findings to another psychostimulant, WAY163909 also attenuated the abuse-related behavioral and neurochemical effects of cocaine. Our findings suggest that serotonin 5-HT2C receptors agonists are effective in reversing the behavioral and neurochemical effects of psychostimulants, being more selective than GABAA receptor modulators.