http://hdl.handle.net/10379/708 Sun, 29 Oct 2017 23:45:23 GMT 2017-10-29T23:45:23Z http://hdl.handle.net/10379/4888 Validation of an air-puff passive-avoidance paradigm for assessment of aversive learning and memory in rat models of chronic pain Moriarty, O,Roche, M,McGuire, BE,Finn, DP Chronic pain is associated with cognitive deficits. Considerable overlap in brain regions involved in pain and aversion suggests that aversive learning and memory may be affected during chronic pain. Passive-avoidance paradigms traditionally use foot-shock to induce context-conditioned avoidance and may be unsuitable for use in animal models of chronic pain, which are commonly associated with hypersensitivity of the hind-paws. The aim of the present study was to develop and validate a novel passive-avoidance paradigm in rats, employing air-puff as the aversive stimulus, and to use this paradigm to assess aversive learning and memory in rat models of chronic inflammatory and neuropathic pain. Air-puff exposure produced a significant passive-avoidance and this response was attenuated following administration of scopolamine. Nerve-ligated rats and rats injected with complete Freund's adjuvant developed allodynia and hyperalgesia. Air-puff produced a significant passive-avoidance response in both chronic pain models. However, there was no difference in the response between either model and its respective control group. Thus, air-puff can be used as an alternative to foot-shock to induce a passive-avoidance response. The data generated using this model suggest that aversive learning and memory remain intact in the rat spinal nerve ligation and complete Freund's adjuvant models of chronic neuropathic and inflammatory pain, respectively. (C) 2011 Elsevier B.V. All rights reserved. Sun, 01 Jan 2012 00:00:00 GMT http://hdl.handle.net/10379/4888 2012-01-01T00:00:00Z http://hdl.handle.net/10379/3943 6-iodonordihydrocapsaicin Roche, Michelle; Finn, David P. 6-Iodonordihydrocapsaicin was first synthesized by Giovanni Appendino at the Department of Chemical, Food, Pharmaceutical and Pharmacological Sciences (DiSCAFF), Novara, Italy, while developing a series of halogenated derivatives of capsaicin (Appendino et al., 2003). This compound is a potent antagonist at the vanilloid VR-1 (TRPV1) receptor in several in vitro preparations. Its activity in vivo has not been examined. Recent evidence indicates that 6-iodonordihydrocapsaicin may also antagonize transient receptor potential channels of melastatin type 8 (TRPM8) (De Petrocellis et al., 2007) Book section (reference) Thu, 01 Jan 2009 00:00:00 GMT http://hdl.handle.net/10379/3943 2009-01-01T00:00:00Z http://hdl.handle.net/10379/3788 The endocannabinoid system and emotional processing: pathophysiology and therapeutic potential. Finn, David P. Although the pharmacological and medicinal properties of the plant Cannabis sativa have long been known and appreciated, the discovery of the endocannabinoid system began with the isolation of [delta]9-tetrahydrocannabinol (THC), the major psychoactive component of the plant, in the mid-1960s (Gaoni and Mechoulam, 1964). Extensive pharmacological studies followed, and, by the end of the last century, the endogenous cannabinoid (endocannabinoid) system was known to comprise at least two metabotropic receptors, cannabinoid receptor types 1 and 2 (CB1 and CB2); two endogenous ligands, the ethanolamine of arachidonic acid, also known as anandamide (AEA), and 2-arachidonoyl-glycerol (2-AG); and the enzymes responsible for their synthesis and catabolism. However, in the last decade (2000-2010), our understanding of the endocannabinoid system has experienced a true revolution. Novel lipid molecules with endocannabinoid activity have been identified; endocannabinoids have been reported to activate additional targets, including the Transient Receptor Potential Vanilloid 1 (TRPV1) channel, nuclear peroxisome proliferator activated receptors (PPARs) and the G protein-coupled receptor GPR55. Moreover, novel pathways for endocannabinoid synthesis and degradation have been discovered. In this special issue, Pamplona and Takahashi (2012) review the discovery of the endocannabinoid system and present the most recent advances in our understanding of the physiology of this system. Journal article Sun, 01 Jan 2012 00:00:00 GMT http://hdl.handle.net/10379/3788 2012-01-01T00:00:00Z http://hdl.handle.net/10379/3511 Pharmacological inhibition of monoacylglycerol lipase attenuates LPS-induced increases in cytokine expression in the rat frontal cortex and plasma: differential mechanisms of action Kerr, Danny; Harhen, Brendan; Egan, Jonathan; Finn, David P.; Roche, Michelle Background and purpose: This study determined the effect of JZL184, a selective inhibitor of monoacylglycerol lipase (MAGL), the enzyme which preferentially catabolises the endocannabinoid 2-arachidonoyl glycerol (2-AG), on inflammatory cytokines in the brain and plasma following an acute immune challenge. The receptor and molecular mechanisms involved were also investigated.Experimental approach: JZL184 and/or AM251 (CB1 antagonist) or AM630 (CB2 antagonist) were administered to rats 30 min prior to the administration of lipopolysaccharide (LPS), 2hrs following which cytokine expression/levels, MAGL activity, 2-AG, arachidonic acid and prostaglandin levels were measured in the frontal cortex, plasma and spleen.Key Results: JZL184 attenuated LPS-induced increases in IL-1β, IL-6, TNF-α and IL-10, but not IĸBα expression in the rat frontal cortex. AM251 attenuated the JZL184-induced decrease in frontal cortical IL-1β expression. Although arachidonic acid levels in the frontal cortex were reduced in JZL184-treated rats, MAGL activity, 2-AG, PGE2 and PGD2 levels remained unchanged. In comparison, MAGL activity was inhibited and 2-AG levels enhanced in the spleen following JZL184 administration. In the plasma, LPS-induced increases in TNF-α and IL-10 levels were attenuated by JZL184, an effect partially blocked by AM251. In addition, AM630 blocked the LPS-induced increases in plasma IL-1β in the presence, but not absence, of JZL184.Conclusion and Implications: Inhibition of peripheral MAGL in the rat by JZL184 suppresses LPS-induced circulating cytokines which in turn may modulate central cytokine expression. The data provide further evidence for the therapeutic potential of targeting the endocannabinoid system for the treatment of central and peripheral inflammatory disorders. Tue, 01 Jan 2013 00:00:00 GMT http://hdl.handle.net/10379/3511 2013-01-01T00:00:00Z