Browsing by Subject "D2"
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Item Pharmacological Evaluation of the D2 and D3 Dopamine Receptor Selective Compounds on L-Dopa Dependent Abnormal Involuntary Movements in Rats(2008-05-01) Kumar, Rakesh; Robert Luedtke; Hriday K. Das; Nathalie SumienKumar Rakesh, Pharmacological Evaluation of the D2 and D3 Dopamine Receptor Selective Compounds on L-dopa Dependent Abnormal Involuntary Movements in Rats. Master of Science (Pharmacology & Neuroscience), May 2008, 106 pp, 21 illustrations, references, 31 titles. Parkinson’s Disease (PD) is a progressive, neurodegenerative disease of the dopamine neurons that innervate the striatum and is characterized by resting tremor, rigidity, bardykinesia and postural instability. L-dopa treatment is the most common and effective therapy for PD. However, both motor (wear-off phenomena, rigidity and dyskinesia) and non-motor (sweating, tachycardia, restless leg syndrome, anxiety, depression, confusion, reduced alertness, psychosis and/or dementia) side effects are associated with long term L-dopa therapy. Motor complications depend on the duration of L-dopa treatment and the abnormal involuntary movements are known as L-dopa-induced dyskinesia (LID). Several studies have suggested a possible role of the dopamine D3 receptor subtype in LID. Here I evaluated the effects of various D2 and D3 dopamine receptor selective compounds on LID in 6-hydroxydopamine-induced complete lesioned hemi-parkinsonian model of rat. D3 dopamine receptor selective compounds (agonists, partial agonists or antagonists) have antidyskinetic effects on LID. Co-administration of D3 dopamine receptor agonist and D3 dopamine receptor antagonist has additive effects in attenuating the LID instead of antagonizing the effects of each other in vivo. D3 dopamine receptor selective compounds attenuated apomorphine-induced dyskinesia.Item The Involvement of D1 and D2 Dopamine Receptors in Cocaine Self-Administration(1996-06-01) Peltier, Rachel; Michael Forster; Patricia A. Gwirtz; Thomas YorioPeltier, Rachel L., The Involvement of D1 and D2 Dopamine Receptors in Cocaine Self-Administration. Doctor of Philosophy (Biomedical Sciences), June 1996, 195 pp. introduction, 6 chapters, discussion, bibliography, 91 titles. D1 and D2 dopamine receptor subtypes have been implicated in producing the reinforcing properties of cocaine. Chronic exposure to cocaine produces tolerance to its reinforcing effects in rats trained to self-administer cocaine. The time between cocaine reinforcers (ISRT) is directly related to dose. A three-point dose-response curve (0.125, 0.25 and 0.5 mg/inj) for cocaine self-administration is obtained during a single test session, allowing determination of optimal tolerance effects of cocaine (20 mg/kg/8 hr/7 days; IP) as demonstrated by a shift of the curve to the right. To test if pharmacokinetic factors contribute to the development of tolerance to the reinforcing properties of cocaine (20 mg/kg/8hr/7days; IP), cocaine and benzoylecgonine (metabolite) were measured in the plasma and brains of rats given a challenge injection of cocaine (2.0 mg/kg; I.V.). Chronic cocaine did not reduce the concentration of cocaine must be due to pharmacodynamics changes. Acute pretreatment with either the direct dopamine agonists d-amphetamine (0.32-3.2 mg/kg) or methamphetamine (1.0 mg/kg) did not consistently change cocaine self-administration. Chronic high-dose treatment with d-amphetamine and methamphetamine produced cross-tolerance to the reinforcing effects of cocaine but apomorphine (0.32-3.2 mg/kg) did not. In contrast, acute pretreatment with dopamine antagonists; flupentixol (mixed D1 and D2, 0.032-1.0 mg/kg), SCH23390 (specific D1, 0.0032-0.32 mg/kg), or eticlopride (specific D2, 0.0032 -3.2 mg/kg); dose-dependently decreased the reinforcing effects of cocaine (ISRT). Chronic treatment with mixed of D1 antagonists (flupentixol, 3.2 mg/kg/12 hr/5 days; or SCH23390, 0.25 mg/kg/12 hr/7 days) produced sensitization to the reinforcing effects of cocaine, but the D2 antagonist eticlopride (0.25 mg/kg/12 hr/7 days) produced cross-tolerance to the reinforcing effects of cocaine. In summary, both the D1 and D2 receptor subtypes seem to be involved in the acute effects of cocaine; however, the development of tolerance to cocaine appears to involve only the D1 receptor subtype.