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FAAH inhibitor, URB-597, promotes extinction and CB(1) antagonist, SR141716, inhibits extinction of conditioned aversion produced by naloxone-precipitated morphine withdrawal, but not extinction of conditioned preference produced by morphine in rats.
Pharmacol Biochem Behav. 2009 Nov; 94(1):154-62.PB

Abstract

Converging evidence suggests that the endogenous cannabinoid (eCB) system is involved in extinction of learned behaviours. Using operant and classical conditioning procedures, the potential of the fatty acid amide (FAAH) inhibitor, URB-597, and the CB(1) antagonist/inverse agonist, SR141716, to promote and inhibit (respectively) extinction of learned responses previously motivated by either rewarding or aversive stimuli was investigated. In the operant conditioning procedure (Expt. 1), rats previously trained to lever press for sucrose reward were administered URB-597 (0.3 mg/kg) or the CB(1) antagonist/inverse agonist SR141716 (2.5 mg/kg) prior to each of three extinction trials. In the conditioned floor preference procedure (Expts 2a-d), rats trained to associate morphine with one of two distinctive floors were administered one of several doses of the CB(1) antagonist/inverse agonist, AM-251 (Expt 2a) or URB-597 (Expt 2b and 2d) prior to each extinction/test trial wherein a choice of both floors was presented and prior to forced exposure to each floor (Expt 2c). In the conditioned floor aversion procedure (Expt. 3), rats trained to associate a naloxone-precipitated morphine withdrawal with a floor cue were administered URB-597 or SR141716 prior to each of 24 extinction/testing trials. URB-597 did not promote and SR141716 did not reduce extinction rates for sucrose reward-induced operant responding (Expt. 1) or morphine-induced conditioned floor preference (Expts. 2a-d). In contrast, URB-597 facilitated, whereas SR141716 impaired, extinction of the conditioned floor aversion (Expt. 3). These data support previous reports that the eCB system selectively facilitates extinction of aversive memories. URB-597 may prove useful in targeting extinction of aversively motivated behaviours.

Authors+Show Affiliations

Department of Psychology, University of Guelph, Guelph, ON N1G2W1, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19698735

Citation

Manwell, Laurie A., et al. "FAAH Inhibitor, URB-597, Promotes Extinction and CB(1) Antagonist, SR141716, Inhibits Extinction of Conditioned Aversion Produced By Naloxone-precipitated Morphine Withdrawal, but Not Extinction of Conditioned Preference Produced By Morphine in Rats." Pharmacology, Biochemistry, and Behavior, vol. 94, no. 1, 2009, pp. 154-62.
Manwell LA, Satvat E, Lang ST, et al. FAAH inhibitor, URB-597, promotes extinction and CB(1) antagonist, SR141716, inhibits extinction of conditioned aversion produced by naloxone-precipitated morphine withdrawal, but not extinction of conditioned preference produced by morphine in rats. Pharmacol Biochem Behav. 2009;94(1):154-62.
Manwell, L. A., Satvat, E., Lang, S. T., Allen, C. P., Leri, F., & Parker, L. A. (2009). FAAH inhibitor, URB-597, promotes extinction and CB(1) antagonist, SR141716, inhibits extinction of conditioned aversion produced by naloxone-precipitated morphine withdrawal, but not extinction of conditioned preference produced by morphine in rats. Pharmacology, Biochemistry, and Behavior, 94(1), 154-62. https://doi.org/10.1016/j.pbb.2009.08.002
Manwell LA, et al. FAAH Inhibitor, URB-597, Promotes Extinction and CB(1) Antagonist, SR141716, Inhibits Extinction of Conditioned Aversion Produced By Naloxone-precipitated Morphine Withdrawal, but Not Extinction of Conditioned Preference Produced By Morphine in Rats. Pharmacol Biochem Behav. 2009;94(1):154-62. PubMed PMID: 19698735.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FAAH inhibitor, URB-597, promotes extinction and CB(1) antagonist, SR141716, inhibits extinction of conditioned aversion produced by naloxone-precipitated morphine withdrawal, but not extinction of conditioned preference produced by morphine in rats. AU - Manwell,Laurie A, AU - Satvat,Elham, AU - Lang,Stefan T, AU - Allen,Craig P, AU - Leri,Francesco, AU - Parker,Linda A, Y1 - 2009/08/19/ PY - 2009/05/31/received PY - 2009/07/31/revised PY - 2009/08/06/accepted PY - 2009/8/25/entrez PY - 2009/8/25/pubmed PY - 2009/12/18/medline SP - 154 EP - 62 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol. Biochem. Behav. VL - 94 IS - 1 N2 - Converging evidence suggests that the endogenous cannabinoid (eCB) system is involved in extinction of learned behaviours. Using operant and classical conditioning procedures, the potential of the fatty acid amide (FAAH) inhibitor, URB-597, and the CB(1) antagonist/inverse agonist, SR141716, to promote and inhibit (respectively) extinction of learned responses previously motivated by either rewarding or aversive stimuli was investigated. In the operant conditioning procedure (Expt. 1), rats previously trained to lever press for sucrose reward were administered URB-597 (0.3 mg/kg) or the CB(1) antagonist/inverse agonist SR141716 (2.5 mg/kg) prior to each of three extinction trials. In the conditioned floor preference procedure (Expts 2a-d), rats trained to associate morphine with one of two distinctive floors were administered one of several doses of the CB(1) antagonist/inverse agonist, AM-251 (Expt 2a) or URB-597 (Expt 2b and 2d) prior to each extinction/test trial wherein a choice of both floors was presented and prior to forced exposure to each floor (Expt 2c). In the conditioned floor aversion procedure (Expt. 3), rats trained to associate a naloxone-precipitated morphine withdrawal with a floor cue were administered URB-597 or SR141716 prior to each of 24 extinction/testing trials. URB-597 did not promote and SR141716 did not reduce extinction rates for sucrose reward-induced operant responding (Expt. 1) or morphine-induced conditioned floor preference (Expts. 2a-d). In contrast, URB-597 facilitated, whereas SR141716 impaired, extinction of the conditioned floor aversion (Expt. 3). These data support previous reports that the eCB system selectively facilitates extinction of aversive memories. URB-597 may prove useful in targeting extinction of aversively motivated behaviours. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/19698735/FAAH_inhibitor_URB_597_promotes_extinction_and_CB_1__antagonist_SR141716_inhibits_extinction_of_conditioned_aversion_produced_by_naloxone_precipitated_morphine_withdrawal_but_not_extinction_of_conditioned_preference_produced_by_morphine_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(09)00246-9 DB - PRIME DP - Unbound Medicine ER -