ABSTRACTGABAERGIC MECHANISMS UNDERLYING ANXIETY BEHAVIOR IN THE POSTPARTUM RATByStephanie M. MillerPostpartum female rodents are less anxious than diestrous virgins in a number of behavioral paradigms. However, reproductive state effects on anxiety have rarely been studied in the light-dark box, and previous studies have been inconsistent. Therefore, I have readdressed the usefulness of the light-dark box to assess anxiety differences between postpartum and virgin female rats. Postpartum females did exhibit less anxiety behavior in a light-dark box then diestrous virgins, but only when ambient illumination was high. Furthermore, reduced postpartum anxiety in the light-dark box was dependent on both infant contact and GABAA receptor activity. Separating postpartum females from their pups for the four hours prior to light-dark box testing increased their anxiety to the level of diestrous virgins, and inhibiting the GABAA receptor at three different binding sites by using (+)-bicuculline (GABA site), FG-7142 (benzodiazepine site), or pentylenetetrazol (picrotoxin site) revealed that pentylenetetrazol produced the strongest anxiogenic effects, often specifically in postpartum and not diestrous virgin females. To investigate whether natural differences in binding to the GABAA receptor contributes to reduced postpartum anxiety, I used autoradiography assays to analyze binding to the picrotoxin ([35TBPS], benzodiazepine (3H]FNP), and GABA's site ([3H]MUSC]) on the receptor. I investigated six different neural sites where GABA is known to mediate anxiety behavior (mPFC, BST, CeA, Hipp, rPAG, cPAG) in the brains of early postpartum, mid-pregnant, diestrous virgin and sexually naïve male rats to look at reproductive state and sex differences in binding. The only significant difference across my groups in binding in any brain region examined was higher [3H]FNP binding in the brains of diestrous virgins in the DG and CA1 regions of the hippocampus in comparison to virgin males and mid-pregnant females, with no differences compared to postpartum females. Lastly, I used Western blot analysis to determine whether these four groups differed in concentration of subtypes of the alpha subunit, as the picrotoxin binding site is associated with this subunit. I examined content of the a2, a3, and a4 in the same six brain regions used previously and found that male rats had higher content of a2 subunit in the rPAG than did diestrous or postpartum females, and there were otherwise no differences in content of any of the subunits across groups in any brain regions investigated. Results from these three experimental chapters are discussed in relation to reduced anxiety behavior in postpartum rats and to the role that the picrotoxin binding site may play in postpartum anxiety.
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