Antipanic-like effect of esketamine and buprenorphine in rats exposed to acute hypoxia

Autor(es)

Maraschin, Jhonatan Christian ^[1] ; Frias, Alana Tercino ^[1] ; Hernandes, Paloma Molina ^[1] ; Batistela, Matheus Fitipaldi ^[1] ; Martinez, Lucas Motta ^[1] ; Lourenco Joca, Samia Regiane ^{[2, 3]} ; Graeff, Frederico Guilherme ^[4] ; Audi, Elisabeth Aparecida ^[5] ; Carneiro Spera de Andrade, Telma Goncalves ^[6] ; Zangrossi Jr, Helio

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Biomol Sci, Ribeirao Preto, SP - Brazil

^[3] Aarhus Univ, Aarhus Inst Adv Studies AIAS, Aarhus - Denmark

^[4] Behav Neurosci Inst INeC, Ribeirao Preto, SP - Brazil

^[5] State Univ Maringa UEM, Dept Pharmacol & Therapeut, Maringa, Parana - Brazil

^[6] Sao Paulo State Univ UNESP, Sch Sci, Dept Biol Sci, Assis, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Behavioural Brain Research; v. 418, FEB 10 2022.
• Citações Web of Science: 0

Resumo

The antidepressant effect of ketamine has been widely acknowledged and the use of one of its enantiomers, Sketamine (esketamine), has recently been approved for the clinical management of treatment-resistant depression. As with ketamine, the non-selective opioid receptor-interacting drug buprenorphine is reported to have antidepressant and anxiolytic properties in humans and rodents. Given the fact that antidepressant drugs are also first line treatment for panic disorder, it is surprising that the potential panicolytic effect of these compounds has been scarcely (ketamine), or not yet (buprenorphine) investigated. We here evaluated the effects of ketamine (the racemic mixture), esketamine, and buprenorphine in male Wistar rats submitted to a panicogenic challenge: acute exposure to hypoxia (7% O2). We observed that esketamine (20 mg/kg), but not ketamine, decreased the number of escape attempts made during hypoxia, and this effect could be observed even 7 days after the drug administration. A panicolytic-like effect was also observed with MK801, which like esketamine, antagonizes NMDA glutamate receptors. Buprenorphine (0.3 mg/kg) also impaired hypoxia-induced escape, an effect blocked by the non-selective opioid receptor antagonist naloxone, indicating an interaction with classical ligand sites, such as mu and kappa receptors, but not with nociception/orphanin FQ receptors. Altogether, the results suggest that esketamine and buprenorphine cause rapid-onset panicolytic-like effects, and may be alternatives for treating panic disorder, particularly in patients who are refractory to standard pharmacological treatment. (AU)

• Processo FAPESP: 18/00153-5 - Papel dos receptores B2 de bradicinina na modulação de respostas defensivas associadas ao pânico: vias de sinalização intracelular envolvidas e interação com receptores µ-opioide
• Beneficiário: Jhonatan Christian Maraschin
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado