Corticotropin-Releasing Factor and Corticosterone Modulate the Anxiogenic-Like Effects of mCPP

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dc.contributor.advisorMichael Forster
dc.contributor.committeeMemberRobert Luedtke
dc.contributor.committeeMemberPatricia Gwirtz
dc.creatorJenkins, Jennifer A.
dc.date.accessioned2019-08-22T21:43:17Z
dc.date.available2019-08-22T21:43:17Z
dc.date.issued1998-06-01
dc.date.submitted2013-08-27T13:28:54-07:00
dc.description.abstractJenkins, Jennifer A., Corticotropin-Releasing Factor and Corticosterone Modulate the Anxiogenic-Like Effects of mCPP. Doctor of Philosophy (Pharmacology), June 1998, 119 pp., 2 tables, 29 figures, bibliography, 100 titles. The administration of PTZ or mCPP produces anxiety-like behavior as measured by an increase in the percentage of entries into the open arms and the time spent on the open arms of the elevated plus maze (Prunell et al., 1994). Reportedly, PTZ and mCPP substitute for each other in the drug discrimination paradigm (Wallis and Laz, 1998). It is therefore suggested that commonality exists among anxiogenic drugs as perceived by trained animals. Andrews and Stephen (1990) suggested that this overall parallelism is an indication that anxiogenic agents may possess similar properties. Therefore, the question posed is as follows: Is there a common denominator anxiety? The global hypothesis is that the core component of anxiety produced by anxiogenic agents or processes involves stimulation of the HPA axis to release CRF, ACTH and/or CORT. Long Evans rats were trained to discriminate either mCPP (1.4 mg/kg) or PTZ (16mg/kg) from saline in a two-lever choice procedure (FR10) which is food reinforced. Animals were pretreated with CRF, α-helical CRF (a CRF antagonist), two steroid synthesis inhibitors (ketoconazole, KETZ and aminoglutethimide, AMG), CORT or underwent an adrenalectomy prior to behavioral testing in order to test the hypothesis that the release of CRF and/or CORT are components of the discriminate stimulus of the mCPP and/or PTZ. Pretreatment with CRF, KETZ, AMG and an adrenalectomy facilitated mCPP level selection. However in the absence of mCPP neither drug nor adrenalectomy produced drug lever selection. In addition CORT did not alter the mCPP dose response curve. However, CORT replacement therapy returned the does response curve to baseline in adrenalectomized animals. Alpha-helical CRF did not block mCPP discrimination. Unlike mCPP-trained animals, KETZ and AMG decreased PTZ-lever selection in PTZ-trained animals. In addition, CORT enhanced and partially substituted for the discriminative stimulus of PTZ. However, adrenalectomy completely abolished drug lever selection in PTZ animals. To compare the discriminative stimulus effects of mCPP and PTZ, PTZ-trained animals were injected with cumulative doses of mCPP. mCPP-trained animals were injected with cumulative doses of PTZ. mCPP and PTZ minimally substituted for each other. The results suggested that neither CRF nor CORT are components of the discriminative stimulus of mCCP and that the role of the HPA axis in mCPP discrimination maybe be a modulator of the stress response. However, CORT is a component of the discriminative stimulus of PTZ such that CORT is necessary for drug lever selection in PTZ trained animals.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29535
dc.language.isoen
dc.provenance.legacyDownloads0
dc.subjectAnimal Sciences
dc.subjectBehavioral Neurobiology
dc.subjectBehavior and Behavior Mechanisms
dc.subjectCell and Developmental Biology
dc.subjectChemical and Pharmacologic Phenomena
dc.subjectChemicals and Drugs
dc.subjectComparative and Laboratory Animal Medicine
dc.subjectExperimental Analysis of Behavior
dc.subjectLaboratory and Basic Science Research
dc.subjectLife Sciences
dc.subjectMedical Pharmacology
dc.subjectMedicinal Chemistry and Pharmaceutics
dc.subjectMedicine and Health Sciences
dc.subjectMolecular and Cellular Neuroscience
dc.subjectNeuroscience and Neurobiology
dc.subjectOther Chemicals and Drugs
dc.subjectOther Neuroscience and Neurobiology
dc.subjectPharmacology
dc.subjectPsychiatry and Psychology
dc.subjectPsychological Phenomena and Processes
dc.subjectPsychology
dc.subjectSocial and Behavioral Sciences
dc.subjectVeterinary Toxicology and Pharmacology
dc.subjectCorticotropin-releasing factor
dc.subjectcorticosterone
dc.subjectanxiogenic-like effects
dc.subjectmCPP
dc.subjectanxiety-like behavior
dc.subjectLong Evans rats
dc.subjectdrug lever selection
dc.subjectadrenalectomy
dc.subjectPTZ
dc.subjectCORT
dc.titleCorticotropin-Releasing Factor and Corticosterone Modulate the Anxiogenic-Like Effects of mCPP
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplinePharmacology and Neuroscience
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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