Browsing by Subject "sigma receptors"
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Item SIGMA 1 RECEPTOR SELECTIVE LIGAND ATTENUATES SCOPOLAMINE INDUCED IMPAIRMENT IN LEARNING AND MEMORY(2013-04-12) Malik, ManinderPurpose: Cognitive deficit is seen in patients with Alzheimer's disease, Parkinson's disease, after brain traumatic injury and stroke. Cognitive deficit is mainly due to the alteration in the cholinergic pathway. All currently prescribed therapeutic drugs provide only symptomatic relief and become ineffective as the disease progresses. Therefore, additional novel therapeutic agents need to be developed to slow or stop the progressive loss of memory forming cells. In this project, we will focus on characterizing a ligand selective at sigma 1 receptor for neuroprotection. Methods: A filtration-binding assay was used to characterize the binding properties of novel sigma compound at D2 like dopamine receptors and at sigma receptors. C57BL/6J mice injected with scopolamine were used as our experimental model to evaluate the cognitive properties of test drug. The neuroprotective properties were evaluated using water maze, active avoidance test and novel objet recognition tests. Results: Scopolamine treated animals exhibited impaired learning and memory in water maze and active avoidance test. Animals pre-treated with test drug attenuated the scopolamine-mediated effect. Conclusions: Test drug was able to attenuate the scopolamine-induced impairment in learning and memory.Item The Role of Dopamine, Nicotine Acetylcholine, Opioid and Sigma Receptors in Ketamine Self-Administration and Reward(2000-05-01) Stoffel, Stephen A.; Michael Forster; Glenn Dillon; Robert LuedtkeStoffel, Stephen A., The Role of Dopamine, Nicotinic Acetylcholine, Opioid and Sigma Receptors in Ketamine Self-Administration and Reward. Doctor of Philosophy in Pharmacology, May 2000, 114 pp 15 figures, bibliography. The rewarding effects of ketamine were postulated to involve dopaminergic neural tracts modulated by nicotinic, sigma, or opioid receptor mechanisms. In support of the hypothesized involvement of dopamine, an increase in extracellular dopamine was detected in the nucleus accumbens using electrochemical chronoamperometry following intravenous ketamine self-administration. When rats were permitted unlimited access to ketamine via self-administration, a greater concentration of dopamine was detected in the nucleus accumbens than was detected in the nucleus accumbens than was detected when self-administration was limited. In a subsequent set of experiments, the effects of agonists or antagonists of dopaminergic, nicotinic, sigma, or opioid receptors were examined for their effect on ketamine self-administration. Decreases in the rate of self-administration following treatment were interpreted to represent an increase in rewarding effect, whereas increases in self-administered were interpreted as a decrease in rewarding effect. The rate of self-administered intraperitoneally prior to ketamine self-administration sessions, but intravenous BMS181-100 would not substitute for ketamine in the self-administration occurred following intraperitoneal (i.p.) administration of: ketamine, SCH23390 (a D1 receptor antagonist), naloxonazine (a mu opioid receptor antagonist), and mecamylamine, a central nicotinic acetylcholine receptor antagonist. An increase in the rate of ketamine self-administration followed nicotine and dihydrexidine (a D1 receptor agonist) intraperitoneal injection. In previous studies, published in the literature, SCH23390 increased the rate of self-administration of amphetamines and cocaine, indicating a competitive effect on drug reward. However, the current studies indicate that the rewarding effects of ketamine were facilitated by SCH23390. The results are consistent with the hypothesis that the rewarding effects of ketamine are mediated through dopaminergic neural pathways. The rewarding effects of ketamine were facilitated by SCH23390. The results are consistent with the hypothesis that the rewarding effects of ketamine are mediated through dopaminergic neural pathways. The rewarding effects of ketamine may be modulated, in an inhibitory fashion, via sigma receptors, presynaptic D1 receptors, nicotinic acetylcholine receptors, and/or μ opioid receptors. Ligands at nicotinic acetylcholine and dopamine receptors yielded effects opposite to that hypothesized based on their ability to modulate the rewarding effects of other abused chemicals.