Sexually Dimorphic Anxiety-Like Interoceptive Discriminative Stimuli

dc.contributor.advisorWalls, Cleatus
dc.contributor.committeeMemberDowney, H. Fred
dc.contributor.committeeMemberForster, Michael
dc.creatorJung, Marianna E.
dc.description.abstractJung, Marianna E., Sexually Dimorphic Anxiety-Like Interoceptive Discriminative Stimuli. Doctor of Philosophy (Biomedical Sciences), December 1997, 150 pp, introduction, 2 chapters, discussion, bibliography, 109 titles. This study compared gender differences in the anxiogenic stimuli induced by either a GABA-A antagonist, pentylenetetrazol (PTZ) or by a 5-HT1b/2 agonist, m-chlorophenylpiperazine (m-CPP) before and during ethanol withdrawal (EW). Rats were trained to discriminate either PTZ (16mg/kg, IP) or m-CPP (1.2 mg/kg, IP) from saline in a two lever choice task for food reward. Male and female rats were gonadectomized or sham-operated, and ovariectomized (OVX) female rats were tested during replacement treatment with 17β estradiol (2.5 mg, 21 day release, sc). The dose-response for the discrimination of the interoceptive stimulus (IDS) produced by PTZ (0-16 mg/kg) or m-CPP (0 to 1.2 mg/kg) was measured under all hormonal conditions. For m-CPP trained rats, latency to first lever-press response was also tested. Results: sham and estradiol-replaced female rats had higher ED50s for discrimination of the PTZ or m-CPP IDS than intact males or OVX rats. There is a dose-related impairment of operant responding after mCPP injection. Sham and estradiol replaced OVX rats showed an increased delay to the initiation of response after m-CPP injection as compared to sham or castrated male rats or OVX rats that showed no effect at the doses tested. Rats then received a chronic ethanol diet (6.5%) for 10 days. At twelve hours of ethanol withdrawl, they were tested for lever selection after saline injection. Fewer sham female and estradiol-replaced female rats responded on the drug lever during acute EW as compared to sham male, castrated or OVX rats. In general, the anxiogenic drug lever selection of OVX rats resembled that of male rats but was restored toward that of sham female rats by estradiol replacement. Castration did not alter the response of male rats to either PTZ or mCPP. Serum β –estradiol concentrations were determined by radioimmunoassay for sham, OVX, and estradiol-replaced female rats. The concentration was significantly higher in hormone-replaced female rats than in OVX. The estradiol concentration in sham female rats showed a cyclic pattern over 4 consecutive days, but this pattern did not correlate with any difference in IDS. Blood ethanol concentration (BEC) was determined using head space gas chromatography. BEC was higher in intact female rats than in intact male rats after ethanol injection (2 g/kg, ip), but did not differ during EW. Conclusions: females produce less anxiogenic IDS in response to either GABA inhibition or 5-HT1b/2 activation, but are more impaired by m-CPP in their ability to initiate operant responses than male rats. In addition, fewer intact females developed a spontaneous IDS during EW than males which is not the result of lower BEC. Estrogen appears to play a trophic role in altering responsiveness to anxiogenic stimuli.
dc.subjectAnimal Sciences
dc.subjectAnimal Structures
dc.subjectBehavioral Neurobiology
dc.subjectBehavior and Behavior Mechanisms
dc.subjectBiochemical and Biomolecular Engineering
dc.subjectCatalysis and Reaction Engineering
dc.subjectCell and Developmental Biology
dc.subjectCell Biology
dc.subjectChemical Actions and Uses
dc.subjectChemicals and Drugs
dc.subjectCognitive Neuroscience
dc.subjectComparative and Laboratory Animal Medicine
dc.subjectEcology and Evolutionary Biology
dc.subjectLife Sciences
dc.subjectMedical Cell Biology
dc.subjectMedicine and Health Sciences
dc.subjectMolecular and Cellular Neuroscience
dc.subjectMolecular Biology
dc.subjectNervous System
dc.subjectNervous System Diseases
dc.subjectNeuroscience and Neurobiology
dc.subjectOther Neuroscience and Neurobiology
dc.subjectOther Nutrition
dc.subjectPharmacy and Pharmaceutical Sciences
dc.subjectPhysiological Processes
dc.subjectReproductive and Urinary Physiology
dc.subjectSignal Processing
dc.subjectStructural Biology
dc.subjectSubstance Abuse and Addiction
dc.subjectSystems and Communications
dc.subjectSystems Neuroscience
dc.subjectVeterinary Toxicology and Pharmacology
dc.subjectSexually dimorphic anxiety-like discriminative stimuli
dc.subjectanxiogenic stimuli
dc.subjectGABA-A antagonist
dc.subjectinteroceptive stimulus
dc.subjectethanol diet
dc.subjectethanol withdrawl
dc.subjectlever selection
dc.subjectsaline injection
dc.subjectestradiol concentration
dc.subjectblood ethanol concentration
dc.subjectGABA inhibition
dc.subject5-HT1b/2 activation
dc.titleSexually Dimorphic Anxiety-Like Interoceptive Discriminative Stimuli
dc.type.materialtext School of Biomedical Sciences Sciences of North Texas Health Science Center at Fort Worth of Philosophy


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