The Involvement of D1 and D2 Dopamine Receptors in Cocaine Self-Administration

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dc.contributor.advisorMichael Forster
dc.contributor.committeeMemberPatricia A. Gwirtz
dc.contributor.committeeMemberThomas Yorio
dc.creatorPeltier, Rachel
dc.date.accessioned2019-08-22T21:22:45Z
dc.date.available2019-08-22T21:22:45Z
dc.date.issued1996-06-01
dc.date.submitted2013-09-23T13:42:07-07:00
dc.description.abstractPeltier, 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.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29287
dc.language.isoen
dc.provenance.legacyDownloads0
dc.subjectBehavior and Behavior Mechanisms
dc.subjectComparative and Laboratory Animal Medicine
dc.subjectLife Sciences
dc.subjectMedical Physiology
dc.subjectMedicine and Health Sciences
dc.subjectOther Pharmacy and Pharmaceutical Sciences
dc.subjectPharmacy and Pharmaceutical Sciences
dc.subjectSubstance Abuse and Addiction
dc.subjectToxicology
dc.subjectD1
dc.subjectD2
dc.subjectDopamine Receptor
dc.subjectCocaine
dc.subjectSelf-Administration
dc.subjectrats
dc.subjectISRT
dc.subjectoptimal tolerance
dc.subjecteffects
dc.titleThe Involvement of D1 and D2 Dopamine Receptors in Cocaine Self-Administration
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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