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1
Content available remote 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
100%
Adamczyk P. , McCreary A. C. , Przegalinski E. , Mierzejewski P. , Bienkowski P. , Filip M.
Journal of Physiology and Pharmacology
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2009
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tom 60
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nr 3
119-125
EN
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.
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Content available remote Activation of endocannabinoid transmission induces antidepressant-like effects in rats
100%
Adamczyk P. , Golda A. , McCreary A. C. , Filip M. , Przegalinski E.
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tom 59
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nr 2
EN
Recent reports indicate that endocannabinoid (eCB) system may be involved in depression and in the antidepressant-like activity demonstrated in experimental models. The present study examined the effects of the eCB uptake inhibitor 4-hydroxyphenyl-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404; 0.1-3 mg/kg), the fatty acid amide hydrolase (FAAH) inhibitor cyclohexylcarbamic acid 3-carbamoylbiphenyl-3-yl ester (URB597; 0.03-0.3 mg/kg), the cannabinoid CB1 receptor agonist (–)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl) phenyl]-trans-4-(3-hydroxypropyl)-cyclohexanol (CP55,940; 0.03-0.3 mg/kg) and the CB1 receptor antagonist rimonabant (0.3-3 mg/kg) on immobility time in the forced swim test (FST) in rats. Moreover, the effects of AM404, CP55,940 and URB597 on the antidepressant-like activity of imipramine and citalopram in the FST were also examined. We found that AM404 (0.3-3 mg/kg), CP55,940 (0.1 mg/kg) and URB597 (0.1-0.3 mg/kg) reduced the immobility time of rats, while rimonabant (0.3-3 mg/kg) was inactive in this respect. We also observed that the anti-immobility effects of AM404 (1 mg/kg), CP55,940 (0.1 mg/kg) and URB597 (0.3 mg/kg), but not of imipramine (30 mg/kg), were blocked by rimonabant (3 mg/kg). In another set of experiments we showed that the inactive dose of AM404 (0.1 mg/kg) potentiated the effects of the inactive doses of imipramine (15 mg/kg) or citalopram (30 mg/kg), while CP55,940 (0.03 mg/kg) and URB597 (0.03 mg/kg) enhanced the effect of imipramine only. None of the drugs studied, given alone or in combination, increased the basal locomotor activity of rats. Our results indicate that activation of the eCB system induces antidepressant-like effects in the FST in rats, and that these effects are mediated by CB1 receptors. Moreover, they also indicate that agents activating eCB transmission enhance the anti-immobility responses to antidepressant drugs.
3
Content available remote A new face of endocannabinoids in pharmacotherapy. Part II: Role of endocannabinoids in inflammation-derived cardiovascular diseases infarction
84%
Zubrzycki M. , Liebold A. , Janecka A. , Zubrzycka M.
Journal of Physiology and Pharmacology
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2014
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tom 65
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nr 2
4
Content available remote Effects of the cannabinoid receptor ligands on anxiety-related effects of D-amphetamine and nicotine in the mouse elevated plus maze test
84%
Biala G. , Kruk M. , Budzynska B.
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nr 2
113-122
EN
The purpose of the experiments was to examine the anxiety-related effects of d-amphetamine and nicotine, and the possible involvement of the endocannabinoid system. D-amphetamine (2 mg/kg, ip) was administered acutely or daily for 8 days. On the 9th day, mice were challenged with d-amphetamine (2 mg/kg, ip) or nicotine (0.1 mg/kg, sc), and were tested in the elevated plus maze. Additionally, a distinct group of mice was pretreated with an acute (0.1 mg/kg, sc) or subchronic nicotine (6 days), and subjected to nicotine (0.1 mg/kg, sc) or d-amphetamine (2 mg/kg, ip) challenge on the 7th day. The cannabinoid receptor ligands, WIN 55,212-2, a non-selective cannabinoid receptor agonist (0.25; 0.5 and 1 mg/kg, ip) and rimonabant, a CB1 cannabinoid receptor antagonist (0.25; 0.5; 1 and 2 mg/kg, ip) were injected prior to each injection of saline or acute and subchronic d-amphetamine or nicotine. We observed that acute anxiogenic and subchronic anxiolytic effects of both psychostimulants as well as the development of full cross-tolerance to their anxiogenic effects were dose-dependently blunted by ineffective doses of WIN 55,212-2 (0.25 and 0.5 mg/kg) and rimonabant (0.5 and 1 mg/kg). These results provide evidence that the endogenous cannabinoid system is involved in the anxiety-related responses to d-amphetamine and/or nicotine.
5
Content available remote Modulation of the endocannabinoid system by the fatty acid amide hydrolase, monoacylglycerol and diacylglycerol lipase inhibitors as an attractive target for secretory diarrhoea therapy
84%
Wasilewski A. , Misicka A. , Sacharczuk M. , Fichna J.
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nr 4
6
Content available remote A new face of endocannabinoids in pharmacotherapy. Part I: Protective role of endocannabinoids in hypertension and myocardial infarction
84%
Zubrzycki M. , Liebold A. , Janecka A. , Zubrzycka M.
Journal of Physiology and Pharmacology
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2014
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tom 65
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nr 2
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