Browsing by MeSH term "Polyunsaturated Alkamides"
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Publication Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition(Public Library of Science (PLOS), 2011-11-30) Cippitelli, Andrea; Astarita, Giuseppe; Duranti, Andrea; Caprioli, Giovanni; Ubaldi, Massimo; Stopponi, Serena; Kallupi, Marsida; Sagratini, Gianni; Rodríguez de Fonseca, Fernando; Piomelli, Daniele; Ciccocioppo, Roberto; [Cippitelli,A; Ubaldi,M; Stopponi,S; Kallupi,M; Ciccocioppo,R] School of Pharmacy,Pharmacology Unit,University of Camerino,Camerino,Italy. [Astarita,G; Piomelli,D] Department of Pharmacology, University of California Irvine, Irvine, California, United States of America. [Duranti,A] Department of Biomolecular Sciences, Medicinal Chemistry and Technology Unit, University of Urbino Carlo Bo, Urbino, Italy. [Caprioli,G; Sagratini,G] School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, Camerino,Italy. [Rodríguez de Fonseca,F] Fundación IMABIS, Hospital Carlos Haya de Málaga, Málaga, Spain. [Piomelli,D] Drug Discovery and Development, Italian Institute of Technology, Genova, Italy.Evidence shows that the endocannabinoid system modulates the addictive properties of nicotine. In the present study, we hypothesized that spontaneous withdrawal resulting from removal of chronically implanted transdermal nicotine patches is regulated by the endocannabinoid system. A 7-day nicotine dependence procedure (5.2 mg/rat/day) elicited occurrence of reliable nicotine abstinence symptoms in Wistar rats. Somatic and affective withdrawal signs were observed at 16 and 34 hours following removal of nicotine patches, respectively. Further behavioral manifestations including decrease in locomotor activity and increased weight gain also occurred during withdrawal. Expression of spontaneous nicotine withdrawal was accompanied by fluctuation in levels of the endocannabinoid anandamide (AEA) in several brain structures including the amygdala, the hippocampus, the hypothalamus and the prefrontal cortex. Conversely, levels of 2-arachidonoyl-sn-glycerol were not significantly altered. Pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for the intracellular degradation of AEA, by URB597 (0.1 and 0.3 mg/kg, i.p.), reduced withdrawal-induced anxiety as assessed by the elevated plus maze test and the shock-probe defensive burying paradigm, but did not prevent the occurrence of somatic signs. Together, the results indicate that pharmacological strategies aimed at enhancing endocannabinoid signaling may offer therapeutic advantages to treat the negative affective state produced by nicotine withdrawal, which is critical for the maintenance of tobacco use.Publication Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition.(Public Library of Science (PLOS), 2011-11-30) Cippitelli, Andrea; Astarita, Giuseppe; Duranti, Andrea; Caprioli, Giovanni; Ubaldi, Massimo; Stopponi, Serena; Kallupi, Marsida; Sagratini, Gianni; Rodríguez de Fonseca, Fernando; Piomelli, Daniele; Ciccocioppo, Roberto; [Cippitelli,A; Ubaldi,M; Stopponi,S; Kallupi,M; Ciccocioppo,R] School of Pharmacy,Pharmacology Unit,University of Camerino,Camerino,Italy. [Astarita,G; Piomelli,D] Department of Pharmacology, University of California Irvine, Irvine, California, United States of America. [Duranti,A] Department of Biomolecular Sciences, Medicinal Chemistry and Technology Unit, University of Urbino ‘‘Carlo Bo’’, Urbino, Italy. [Caprioli,G; Sagratini,G] School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, Camerino,Italy. [Rodríguez de Fonseca,F] Fundación IMABIS, Hospital Carlos Haya de Málaga, Málaga, Spain. [Piomelli,D] Drug Discovery and Development, Italian Institute of Technology, Genova, Italy.Evidence shows that the endocannabinoid system modulates the addictive properties of nicotine. In the present study, we hypothesized that spontaneous withdrawal resulting from removal of chronically implanted transdermal nicotine patches is regulated by the endocannabinoid system. A 7-day nicotine dependence procedure (5.2 mg/rat/day) elicited occurrence of reliable nicotine abstinence symptoms in Wistar rats. Somatic and affective withdrawal signs were observed at 16 and 34 hours following removal of nicotine patches, respectively. Further behavioral manifestations including decrease in locomotor activity and increased weight gain also occurred during withdrawal. Expression of spontaneous nicotine withdrawal was accompanied by fluctuation in levels of the endocannabinoid anandamide (AEA) in several brain structures including the amygdala, the hippocampus, the hypothalamus and the prefrontal cortex. Conversely, levels of 2-arachidonoyl-sn-glycerol were not significantly altered. Pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for the intracellular degradation of AEA, by URB597 (0.1 and 0.3 mg/kg, i.p.), reduced withdrawal-induced anxiety as assessed by the elevated plus maze test and the shock-probe defensive burying paradigm, but did not prevent the occurrence of somatic signs. Together, the results indicate that pharmacological strategies aimed at enhancing endocannabinoid signaling may offer therapeutic advantages to treat the negative affective state produced by nicotine withdrawal, which is critical for the maintenance of tobacco use.Publication Exposure to a Highly Caloric Palatable Diet During Pregestational and Gestational Periods Affects Hypothalamic and Hippocampal Endocannabinoid Levels at Birth and Induces Adiposity and Anxiety-Like Behaviors in Male Rat Offspring.(Frontiers Media, 2016-01-06) Ramírez-López, María Teresa; Vázquez, Mariam; Bindila, Laura; Lomazzo, Ermelinda; Hofmann, Clementine; Blanco, Rosario Noemí; Alén, Francisco; Antón, María; Decara, Juan; Ouro, Daniel; Orio, Laura; Suarez, Juan; Lutz, Beat; Rodríguez de Fonseca, Fernando; Gómez de Heras, Raquel; [Ramírez-López,MT; Vázquez,M; Blanco,RN; Alén,F; Antón,M; Ouro,L; Rodríguez de Fonseca,F; Gómez de Heras,R] Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, Madrid, Spain. [Vázquez,M; Degara,J; Suarez,J; Rodríguez de Fonseca,F] Unidad de Gestión Clínica de Salud Mental, Instituto IBIMA, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain. [Bindila,L; Lomazzo,E; Hofmann,C; Lutz,B] Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.Exposure to unbalanced diets during pre-gestational and gestational periods may result in long-term alterations in metabolism and behavior. The contribution of the endocannabinoid system to these long-term adaptive responses is unknown. In the present study, we investigated the impact of female rat exposure to a hypercaloric-hypoproteic palatable diet during pre-gestational, gestational and lactational periods on the development of male offspring. In addition, the hypothalamic and hippocampal endocannabinoid contents at birth and the behavioral performance in adulthood were investigated. Exposure to a palatable diet resulted in low weight offspring who exhibited low hypothalamic contents of arachidonic acid and the two major endocannabinoids (anandamide and 2-arachidonoylglycerol) at birth. Palmitoylethanolamide, but not oleoylethanolamide, also decreased. Additionally, pups from palatable diet-fed dams displayed lower levels of anandamide and palmitoylethanolamide in the hippocampus. The low-weight male offspring, born from palatable diet exposed mothers, gained less weight during lactation and although they recovered weight during the post-weaning period, they developed abdominal adiposity in adulthood. These animals exhibited anxiety-like behavior in the elevated plus-maze and open field test and a low preference for a chocolate diet in a food preference test, indicating that maternal exposure to a hypercaloric diet induces long-term behavioral alterations in male offspring. These results suggest that maternal diet alterations in the function of the endogenous cannabinoid system can mediate the observed phenotype of the offspring, since both hypothalamic and hippocampal endocannabinoids regulate feeding, metabolic adaptions to caloric diets, learning, memory, and emotions.