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A role for the mu opioid receptor in the antidepressant effects of buprenorphine.
Robinson, Shivon A; Erickson, Rebecca L; Browne, Caroline A; Lucki, Irwin.
Afiliação
  • Robinson SA; Departments of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, United States.
  • Erickson RL; Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, United States.
  • Browne CA; Departments of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, United States.
  • Lucki I; Departments of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, United States; Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, United States. Electronic address: irwin.lucki@usuhs.edu.
Behav Brain Res ; 319: 96-103, 2017 02 15.
Article em En | MEDLINE | ID: mdl-27818236
Buprenorphine (BPN), a mixed opioid drug with high affinity for mu (MOR) and kappa (KOR) opioid receptors, has been shown to produce behavioral responses in rodents that are similar to those of antidepressant and anxiolytic drugs. Although recent studies have identified KORs as a primary mediator of BPN's effects in rodent models of depressive-like behavior, the role of MORs in BPN's behavioral effects has not been as well explored. The current studies investigated the role of MORs in mediating conditioned approach behavior in the novelty-induced hypophagia (NIH) test, a behavioral measure previously shown to be sensitive to chronic treatment with antidepressant drugs. The effects of BPN were evaluated in the NIH test 24h post-administration in mice with genetic deletion of the MOR (Oprm1-/-) or KOR (Oprk1-/-), or after pharmacological blockade with the non-selective opioid receptor antagonist naltrexone and selective MOR antagonist cyprodime. We found that behavioral responses to BPN in the NIH test were blocked in Oprm1-/- mice, but not in Oprk1-/- mice. Both cyprodime and naltrexone significantly reduced approach latency at doses experimentally proven to antagonize the MOR. In contrast the selective MOR agonist morphine and the selective KOR antagonist nor-BNI were both ineffective. Moreover, antinociceptive studies revealed persistence of the MOR antagonist properties of BPN at 24h post-administration, the period of behavioral reactivity. These data support modulation of MOR activity as a key component of BPN's antidepressant-like effects in the NIH paradigm.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Comportamento Animal / Buprenorfina / Transtornos da Alimentação e da Ingestão de Alimentos / Receptores Opioides mu / Antidepressivos Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Comportamento Animal / Buprenorfina / Transtornos da Alimentação e da Ingestão de Alimentos / Receptores Opioides mu / Antidepressivos Idioma: En Ano de publicação: 2017 Tipo de documento: Article