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The effects of fatty acid amide hydrolase inhibitors on maintenance of cocaine and food self-administration and on reinstatement of cocaine-seeking and food-taking behavior in rats.
J Physiol Pharmacol. 2009 Sep; 60(3):119-25.JP

Abstract

Some empirical evidence suggests that the endocannabinoids (eCB) (e.g. anandamide) may play an important role in cocaine addiction. The eCB act as a retrograde messengers activating CB receptors at the presynaptic membrane and are degraded by enzymatic actions of fatty acid amide hydrolase (FAAH). The present study aimed to examine the effect of the FAAH inhibitors, phenylmethylsulphonyl fluoride (PMSF; i.p.) or cyclohexylcarbamic acid 3-carbamoyl biphenyl-3-yl ester (URB597; i.p.) on the cocaine- or food-maintained self-administration as well as on the cocaine-seeking or food-taking behaviors in rats. Male Wistar rats were implanted with a catheter (iv.) and trained to self-administer cocaine (0.5 mg/kg/infusion) on a fixed ratio 5 schedule of reinforcement with a conditioned stimulus (tone+light). After self-administration stabilized, extinction/reinstatement procedures were carried out during which the rats were tested for the response reinstatement induced by cocaine (10 mg/kg, ip) or a cue (light+tone). The food (sweetened milk) self-administration and extinction/reinstatement procedures were conducted in a manner resembling cocaine self-administration. Neither PMSF (30-120 mg/kg) nor URB597 (0.1-3 mg/kg) affected cocaine self-administration. PMSF, 60 mg/kg, significantly reduced cocaine-induced reinstatement and at 120 mg/kg (combined with the challenge dose of cocaine) it evoked behavioral disruption. PMSF (60-120 mg/kg) dose-dependently inhibited cue-induced reinstatement. URB597 (1-3 mg/kg) attenuated both cocaine- and cue-induced drug-seeking behaviors. PMSF (60 mg/kg) decreased food self-administration. Toward reinstatement of food-taking behavior PMSF (60-120 mg/kg) and URB597 (3 mg/kg) showed inhibitory effects. Our results indicate that FAAH inhibitors could be potent modulators of motivational and conditioned aspects of goal-directed behaviors with less prominent effects on consumatory behaviors.

Authors+Show Affiliations

Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland.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

19826190

Citation

Adamczyk, P, et al. "The Effects of Fatty Acid Amide Hydrolase Inhibitors On Maintenance of Cocaine and Food Self-administration and On Reinstatement of Cocaine-seeking and Food-taking Behavior in Rats." Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, vol. 60, no. 3, 2009, pp. 119-25.
Adamczyk P, McCreary AC, Przegalinski E, et al. The effects of fatty acid amide hydrolase inhibitors on maintenance of cocaine and food self-administration and on reinstatement of cocaine-seeking and food-taking behavior in rats. J Physiol Pharmacol. 2009;60(3):119-25.
Adamczyk, P., McCreary, A. C., Przegalinski, E., Mierzejewski, P., Bienkowski, P., & Filip, M. (2009). The effects of fatty acid amide hydrolase inhibitors on maintenance of cocaine and food self-administration and on reinstatement of cocaine-seeking and food-taking behavior in rats. Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, 60(3), 119-25.
Adamczyk P, et al. The Effects of Fatty Acid Amide Hydrolase Inhibitors On Maintenance of Cocaine and Food Self-administration and On Reinstatement of Cocaine-seeking and Food-taking Behavior in Rats. J Physiol Pharmacol. 2009;60(3):119-25. PubMed PMID: 19826190.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of fatty acid amide hydrolase inhibitors on maintenance of cocaine and food self-administration and on reinstatement of cocaine-seeking and food-taking behavior in rats. AU - Adamczyk,P, AU - McCreary,A C, AU - Przegalinski,E, AU - Mierzejewski,P, AU - Bienkowski,P, AU - Filip,M, PY - 2008/09/22/received PY - 2009/07/15/accepted PY - 2009/10/15/entrez PY - 2009/10/15/pubmed PY - 2010/3/31/medline SP - 119 EP - 25 JF - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society JO - J. Physiol. Pharmacol. VL - 60 IS - 3 N2 - Some empirical evidence suggests that the endocannabinoids (eCB) (e.g. anandamide) may play an important role in cocaine addiction. The eCB act as a retrograde messengers activating CB receptors at the presynaptic membrane and are degraded by enzymatic actions of fatty acid amide hydrolase (FAAH). The present study aimed to examine the effect of the FAAH inhibitors, phenylmethylsulphonyl fluoride (PMSF; i.p.) or cyclohexylcarbamic acid 3-carbamoyl biphenyl-3-yl ester (URB597; i.p.) on the cocaine- or food-maintained self-administration as well as on the cocaine-seeking or food-taking behaviors in rats. Male Wistar rats were implanted with a catheter (iv.) and trained to self-administer cocaine (0.5 mg/kg/infusion) on a fixed ratio 5 schedule of reinforcement with a conditioned stimulus (tone+light). After self-administration stabilized, extinction/reinstatement procedures were carried out during which the rats were tested for the response reinstatement induced by cocaine (10 mg/kg, ip) or a cue (light+tone). The food (sweetened milk) self-administration and extinction/reinstatement procedures were conducted in a manner resembling cocaine self-administration. Neither PMSF (30-120 mg/kg) nor URB597 (0.1-3 mg/kg) affected cocaine self-administration. PMSF, 60 mg/kg, significantly reduced cocaine-induced reinstatement and at 120 mg/kg (combined with the challenge dose of cocaine) it evoked behavioral disruption. PMSF (60-120 mg/kg) dose-dependently inhibited cue-induced reinstatement. URB597 (1-3 mg/kg) attenuated both cocaine- and cue-induced drug-seeking behaviors. PMSF (60 mg/kg) decreased food self-administration. Toward reinstatement of food-taking behavior PMSF (60-120 mg/kg) and URB597 (3 mg/kg) showed inhibitory effects. Our results indicate that FAAH inhibitors could be potent modulators of motivational and conditioned aspects of goal-directed behaviors with less prominent effects on consumatory behaviors. SN - 1899-1505 UR - https://www.unboundmedicine.com/medline/citation/19826190/The_effects_of_fatty_acid_amide_hydrolase_inhibitors_on_maintenance_of_cocaine_and_food_self_administration_and_on_reinstatement_of_cocaine_seeking_and_food_taking_behavior_in_rats_ L2 - http://www.jpp.krakow.pl/journal/archive/09_09/pdf/119_09_09_article.pdf DB - PRIME DP - Unbound Medicine ER -