Respiratory effects of buprenorphine/naloxone alone and in combination with diazepam in naive and tolerant rats

•Like buprenorphine alone, buprenorphine/naloxone does not depress ventilation in rats.•IV buprenorphine/naloxone injection induces withdrawal symptoms in tolerant rats.•Naloxone does not prevent the deleterious respiratory effects of buprenorphine/diazepam. Respiratory depression has been attributed to buprenorphine (BUP) misuse or combination with benzodiazepines. BUP/naloxone (NLX) has been marketed as maintenance treatment, aiming at preventing opiate addicts from self-injecting crushed pills. However, to date, BUP/NLX benefits in comparison to BUP alone remain debated. We investigated the plethysmography effects of BUP/NLX in comparison to BUP/solvent administered by intravenous route in naive and BUP-tolerant Sprague-Dawley rats, and in combination with diazepam (DZP) or its solvent. In naive rats, BUP/NLX in comparison to BUP significantly increased respiratory frequency (f, P