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    Sexually Dimorphic Anxiety-Like Interoceptive Discriminative Stimuli

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    Date
    1997-12-01
    Author
    Jung, Marianna E.
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    Abstract
    Jung, 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.
    Subject
    Animal Sciences
    Animal Structures
    Behavioral Neurobiology
    Behavior and Behavior Mechanisms
    Biochemical and Biomolecular Engineering
    Biochemistry
    Biology
    Biomedical
    Catalysis and Reaction Engineering
    Cell and Developmental Biology
    Cell Biology
    Chemical Actions and Uses
    Chemicals and Drugs
    Cognitive Neuroscience
    Comparative and Laboratory Animal Medicine
    Ecology and Evolutionary Biology
    Life Sciences
    Medical Cell Biology
    Medicine and Health Sciences
    Molecular and Cellular Neuroscience
    Molecular Biology
    Nervous System
    Nervous System Diseases
    Neuroscience and Neurobiology
    Neurosciences
    Other Neuroscience and Neurobiology
    Other Nutrition
    Pharmacy and Pharmaceutical Sciences
    Physiological Processes
    Reproductive and Urinary Physiology
    Signal Processing
    Structural Biology
    Substance Abuse and Addiction
    Systems and Communications
    Systems Neuroscience
    Therapeutics
    Veterinary Toxicology and Pharmacology
    Sexually dimorphic anxiety-like discriminative stimuli
    anxiogenic stimuli
    GABA-A antagonist
    pentylenetetrazol
    m-chlorophenylpiperazine
    gonadectomize
    ovariectomize
    interoceptive stimulus
    ethanol diet
    ethanol withdrawl
    lever selection
    saline injection
    estradiol concentration
    blood ethanol concentration
    GABA inhibition
    5-HT1b/2 activation
    URI
    https://hdl.handle.net/20.500.12503/29354
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    • School of Biomedical Sciences
    • Theses and Dissertations

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