title: Benzodiazepines increase the reward effects of buprenorphine in a conditioned place preference test in the mouse.
abstract: Buprenorphine (BPN) is widely used as a substitution treatment for opioid addiction. Some cases of abuse and misuse, especially associated with various benzodiazepines (BZDs), have been described, and a previous study has shown that BZDs increase the sedative effect of BPN and decrease its anxiogenic properties. To investigate the reward effect that may lead to the abusive combination of BPN and BZD, we studied the influence of different doses of three BZDs extensively used with BPN by drug addicts on conditioned place preference behavior in mice. BPN (0.3, 1, 3 mg/kg) was injected subcutaneously into male mice alone or in combination with a BZD administered intraperitoneally: dipotassium clorazepate (CRZ; 1, 4, 16 mg/kg), diazepam (DAZ; 0.5, 1, 5 mg/kg), or bromazepam (BMZ; 0.5, 1, 3 mg/kg). Amphetamine (8 mg/kg) was used as a reference drug. Reward effects of BPN alone or in combination were measured in a conditioned place preference paradigm using an unbiased procedure. Our results showed that groups treated with BPN associated with different doses of diazepam and clorazepate, but not bromazepam, spent significantly more time in the drug-paired compartment compared to the group treated with BPN alone. Our study shows that joint consumption of diazepam and clorazepate, but not bromazepam, can increase the reward properties of BPN alone in mice. These results could help to explain the use of this type of drug combination in the drug addict population.
authors.affiliation: Normandie University, CS 14032, Cedex 5, Caen, France; UCBN, COMETE, UFR de Médecine, Avenue de la Côte de Nacre, CS 14032, Cedex 5, Caen, France; Inserm, U 1075 COMETE, UFR de Médecine, Avenue de la Côte de Nacre, CS 14032, Cedex 5, Caen, France.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Ma
authors.forename: Thomas
authors.initials: T
authors.lastname: Freret
authors.forename: Mathilde
authors.initials: M
authors.lastname: Lange
authors.forename: Joanna
authors.initials: J
authors.lastname: Bourgine
authors.forename: Antoine
authors.initials: A
authors.lastname: Coquerel
authors.forename: Véronique
authors.initials: V
authors.lastname: Lelong-Boulouard
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001960:Bromazepam / Q000008:administration & dosage / Q000494:pharmacology*; D002047:Buprenorphine / Q000008:administration & dosage / Q000494:pharmacology*; D003009:Clorazepate Dipotassium / Q000008:administration & dosage / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D012201:Reward
chemical_list: D002047:Buprenorphine; D003009:Clorazepate Dipotassium; D000661:Amphetamine; D003975:Diazepam; D001960:Bromazepam
keywords: addiction; benzodiazepines; buprenorphine; conditioned place preference; opioid substitution treatment