RATIONALE: Modulation of the endocannabinoid system has been found to interfere with opiate withdrawal. The potential of activation and blockade of the endocannabinoid system to prevent the aversive-affective state of naloxone-precipitated morphine withdrawal (MWD) was investigated in a one-trial conditioned place aversion (CPA) paradigm. OBJECTIVE: CPA provides a sensitive measure of the motivational effects of acute MWD. The potential of the fatty acid amide hydrolase (FAAH) inhibitors, URB597 and PF-3845, the CB1 antagonist/inverse agonist, AM251, and the neutral CB1 antagonists, AM4113 and AM6527 (oral), to interfere with establishment of a MWD-induced CPA was investigated. As well, the potential of AM251 and AM4113 to interfere with reinstatement of a previously established MWD-induced CPA was investigated. MATERIALS AND METHODS: Using a one-trial place conditioning paradigm, rats were administered naloxone (1 mg/kg, subcutaneous (s.c.)) 24 h after receiving a high dose of morphine (20 mg/kg, s.c.) and were placed on the conditioning floor. To determine the effect of each pretreatment drug on the establishment of the MWD-induced CPA, URB597 (0.3 mg/kg, intraperitoneally (i.p.)), PF-3845 (10 mg/kg, i.p.), AM251 (1 or 2.5 mg/kg, i.p.), AM4113 (1 or 2.5 mg/kg, i.p.), and AM6527 (5 mg/kg, oral) were administered prior to conditioning. RESULTS: AM251 (2.5, but not 1 mg/k), AM4113, and AM6527, but not URB597 or PF-3845, interfered with the establishment of the MWD-induced CPA. AM251 and AM4113 did not prevent reinstatement of the CPA. CONCLUSIONS: Neutral antagonism of the CB1 receptor reduces the aversive affective properties of morphine withdrawal.
RATIONALE: Modulation of the endocannabinoid system has been found to interfere with opiate withdrawal. The potential of activation and blockade of the endocannabinoid system to prevent the aversive-affective state of naloxone-precipitated morphine withdrawal (MWD) was investigated in a one-trial conditioned place aversion (CPA) paradigm. OBJECTIVE:CPA provides a sensitive measure of the motivational effects of acute MWD. The potential of the fatty acid amide hydrolase (FAAH) inhibitors, URB597 and PF-3845, the CB1 antagonist/inverse agonist, AM251, and the neutral CB1 antagonists, AM4113 and AM6527 (oral), to interfere with establishment of a MWD-induced CPA was investigated. As well, the potential of AM251 and AM4113 to interfere with reinstatement of a previously established MWD-induced CPA was investigated. MATERIALS AND METHODS: Using a one-trial place conditioning paradigm, rats were administered naloxone (1 mg/kg, subcutaneous (s.c.)) 24 h after receiving a high dose of morphine (20 mg/kg, s.c.) and were placed on the conditioning floor. To determine the effect of each pretreatment drug on the establishment of the MWD-induced CPA, URB597 (0.3 mg/kg, intraperitoneally (i.p.)), PF-3845 (10 mg/kg, i.p.), AM251 (1 or 2.5 mg/kg, i.p.), AM4113 (1 or 2.5 mg/kg, i.p.), and AM6527 (5 mg/kg, oral) were administered prior to conditioning. RESULTS:AM251 (2.5, but not 1 mg/k), AM4113, and AM6527, but not URB597 or PF-3845, interfered with the establishment of the MWD-induced CPA. AM251 and AM4113 did not prevent reinstatement of the CPA. CONCLUSIONS: Neutral antagonism of the CB1 receptor reduces the aversive affective properties of morphine withdrawal.
Authors: Kiri L Wills; Gavin N Petrie; Geneva Millett; Cheryl L Limebeer; Erin M Rock; Micah J Niphakis; Benjamin F Cravatt; Linda A Parker Journal: Neuropsychopharmacology Date: 2015-12-09 Impact factor: 7.853
Authors: Charles W Schindler; Godfrey H Redhi; Kiran Vemuri; Alexandros Makriyannis; Bernard Le Foll; Jack Bergman; Steven R Goldberg; Zuzana Justinova Journal: Neuropsychopharmacology Date: 2016-02-18 Impact factor: 7.853
Authors: Emily E Thompson; Julia E Jagielo-Miller; V Kiran Vemuri; Alexandros Makriyannis; Peter J McLaughlin Journal: J Psychopharmacol Date: 2016-03-22 Impact factor: 4.153