Thesis (Ph.D.)--Aberdeen University, 2008. / Title from web page (viewed on July 20, 2009). Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 86-98).

Here we demonstrate that both exogenous and endogenous cannabinoids affect different aspects of learning and memory in the rat.  For example, the potent CB₁ receptor agonist, WIN-2 was able to delay-dependently impair short-term memory (STM) sparing reference memory (RM).  This demonstrates that it is the STM but  not RM processes that are more sensitive to the effects of cannabinoids. In addition, given that cannabinoids were able to hinder the recruitment of hippocampal firing correlates that are crucial for correct performance of a STM task, suppress hippocampal principal cell firing during the encoding phase of a STM task, reduce spontaneous bursting and disrupt synchronous firing of hippocampal principal cells respectively, confirm that they do alter the neurophysiology of the hippocampus.  These cannabinoid induced alterations in hippocampal neuronal activity may well explain the observed deficits across numerous other working memory (WM) and STM tasks. The results also revealed that cannabinoid-induced deficits in learning and memory are brought about due to an interaction between cannabinoid and cholinergic systems.  Although endocannabinoids failed to produce impairments in STM under normal physiological conditions, STM deficits were observed when anadamide levels were pharmacologically elevated beyond normal physiological levels.  Moreover, results demonstrate that the endocannabinoid system is involved in behavioural flexibility (i.e. reversal learning) and modulation of acquisition and/or consolidation of certain spatial elements that are necessary to perform an operant conditioning risk. Overall, the results in this thesis show that cannabinoid induced deficits in learning and memory are produced as a result of their direct effects on hippocampal processing.  The exact mechanisms that mediate these cannabinoid-induced deficits in memory are yet unclear and remain to be determined.

Thesis (Ph.D.)--Virginia Commonwealth University, 2009. / Prepared for: Dept. of Pharmacology and Toxicology. Title from title-page of electronic thesis. Bibliography: leaves 130-143.

Diss. (sammanfattning) Umeå : Univ., 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Endocannabinoids are products of phospholipid-derived arachidonic acid that regulate hypothalamus-pituitary-adrenal axis activity. We hypothesize that differences in the quality and quantity of maternal dietary fat will modulate the neonatal phospholipid arachidonic acid content of the brain affecting the stress response via differences in endocannabinoid concentration of stress-activated brain areas. Dams were fed a 5% (C) or 300.10 fat diet rich in either n-6 (C, HF) or n-3 (HFF) fat during the perinatal period. PND4-5 HFF milk displays a reduced n-6/n-3 ratio compared to C and HF milk. PND10 hypothalamic and hippocampal PL AA levels are reduced in HFF pups relative to C and HF offspring; and predict endocannabinoid levels in a region-specific manner. In all pups pre-treated with an endocannabinoid receptor antagonist (AM251) or an inhibitor of the endocannabinoid degradative enzyme (URB597), basal and stress-induced ACTH secretion dose-dependently increased. Moreover, HFF pups exhibited a tendency towards reduced AM251 sensitivity under stressful conditions. These data suggest that the nature of perinatal dietary fat can differentially influence neonatal brain arachidonic acid levels and their endocannabinoid derivatives; and endocannabinoid signaling may be altered between diet groups since pups exhibit differences in sensitivity to endocannabinoid receptor blockade.

No description available.

Orientador: Carlos Amilcar Parada / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-26T11:05:11Z (GMT). No. of bitstreams: 1 DosSantos_GilsonGoncalves_M.pdf: 2757194 bytes, checksum: 3b5bda3ca0fc7912d13b42ba51399734 (MD5) Previous issue date: 2014 / Resumo: A dipirona (metamizol) é um pró-fármaco analgésico utilizado no controle da dor moderada, sendo metabolizada em dois metabolitos bioativos: 4-metil-aminoantipirina (4-MAA) e 4-aminoantipirina (4-AA). O objetivo deste estudo foi investigar a participação de receptores canabinóides periféricos, CB1, CB2 e canais de KATP sobre o efeito anti-hiperalgésico da dipirona, 4-MAA ou 4- AA. Para indução de hiperalgesia, PGE2 (100 ng/pata ) foi administrada localmente na pata traseira de ratos Wistar machos, e o limiar hiperalgésico mecânico foi quantificado por Von- Frey eletrônico, antes e três horas após a injeção. Dipirona, 4-MAA ou 4-AA foram administrados 30 minutos antes do Von Frey. Os antagonistas seletivos do receptor CB1 (AM251), CB2 (AM630) e glibenclamida, um bloqueador KATP (80 ug) ou ODQ um inibidor de cGMP (32 ?g) foram administrados 30 minutos antes da Dipirona, 4-MAA ou 4 -AA. O ODN-antisense para reduzir a expressão do receptor CB1 (30 ?g) foi administrado por via intratecal, uma vez por dia durante quatro dias consecutivos. A hiperalgesia mecânica induzida pela PGE2 foi reduzida pela dipirona, 4-MAA, e 4-AA de maneira dose-dependente. AM251 ou ODN-antisense contra o receptor neuronal CB1, mas não AM630, reduziu o efeito anti-hiperalgésico mediado por 4-AA, mas não da dipirona ou 4-MAA. Por outro lado, o efeito anti-hiperalgésico da dipirona, ou 4-MAA foi revertido por glibenclamida ou ODQ. Os resultados sugerem que a ativação de receptores neuronal CB1, mas não do receptor CB2, no tecido periférico esteja envolvido no efeito anti-hiperalgésico do metabólito 4-AA. Além disso, a dipirona e 4-MAA possui um efeito anti-hiperalgesico dependente de cGMP e consequente abertura KATP / Abstract: Dipyrone (metamizole) is an analgesic pro-drug used to control moderate pain. It is metabolized in two bioactive metabolites: 4-methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA). The aim of this study was to investigate the participation of peripheral CB1 and CB2 cannabinoid receptors activation on the anti-hyperalgesic effect of Dypirone, 4-MAA or 4-AA. For induction of hyperalgesia, PGE2 (100 ng) was locally administrated in hindpaw of male Wistar rats, and the mechanical nociceptive threshold was quantified by electronic von-Frey, before and 3 hours after its injection. Dypirone, 4-MAA or 4-AA was administrated 30 minutes before the von-Frey test. The selective CB1 receptor antagonist AM251, CB2 receptor antagonist AM630, cGMP inhibitor ODQ (32 ?g) or KATP blocker glibenclamide (80 ?g) was administrated 30 minutes before Dypirone, 4-MAA or 4-AA. The antisense-ODN against CB1 receptor expression (30 ?g) was intrathecally administrated once a day during four consecutive days. PGE2-induced mechanical hyperalgesia was inhibited by dypirone, 4-MAA, and 4-AA in a dose-response manner. AM251 or ODN anti-sense against neuronal CB1 receptor, but not AM630, reversed the antihyperalgesic effect mediated by 4-AA, but not by dypirone or 4-MAA. On the other hand, the anti-hyperalgesic effect of dypirone or 4-MAA was reversed by Glibenclamide or ODQ. These results suggest that the activation of neuronal CB1, but not CB2 receptor, in the peripheral tissue is involved in the anti-hyperalgesic effect of 4-aminoantipyrine. In addition, 4- methylaminontipyrine mediates anti-hyperalgesic effect by the cGMP activation and the KATP opening / Mestrado / Fisiologia / Mestre em Biologia Funcional e Molecular