Postpartum State, but Not Maternal Caregiving or Level of Anxiety, Increases Medial Prefrontal Cortex GAD65 and vGAT in Female Rats.

Christina M Ragan,Katrina Linning-Duffy,Erika M Vitale,Stephanie M Miller-Smith,Joseph S Lonstein,Eman I Ahmed,Jamie Maguire

doi:10.3389/fgwh.2021.746518

Abstract

Upregulation of the inhibitory neurotransmitter, GABA, is involved in many of the behavioral differences between postpartum and nulliparous female rodents. This is evidenced by studies showing that pharmacological blockade of GABAergic activity impairs maternal caregiving and postpartum affective behaviors. However, the influence of motherhood on the capacity for GABA synthesis or release in the medial prefrontal cortex (mPFC; brain region involved in many social and affective behaviors) is not well-understood. Western blotting was used to compare postpartum and nulliparous rats in protein levels of the 65-kD isoform of glutamic acid decarboxylase (GAD65; synthesizes most GABA released from terminals) and vesicular GABA transporter (vGAT; accumulates GABA into synaptic vesicles for release) in the mPFC. We found that postpartum mothers had higher GAD65 and vGAT compared to virgins, but such differences were not found between maternally sensitized and non-sensitized virgins, indicating that reproduction rather than just the display of maternal caregiving is required. To test whether GAD65 and vGAT levels in the mPFC were more specifically related to anxiety-related behavior within postpartum mothers, we selected 8 low-anxiety and 8 high-anxiety dams based on their time spent in the open arms of an elevated plus maze on postpartum day 7. There were no significant differences between the anxiety groups in either GAD65 or vGAT levels. These data further indicate that frontal cortical GABA is affected by female reproduction and more likely contributes to differences in the display of socioemotional behaviors across, but not within, female reproductive state.

Highlights

The early postpartum period is associated with a number of salient behavioral modifications including elevated interest in neonates, the performance of caregiving activities, and a suppression of anxiety- and fear-related behaviors that facilitates mothers’ positive focus on the offspring [for reviews see [1, 2]]
Studies exploring differences between parous and nulliparous female laboratory rodents in their central GABAA or benzodiazepine receptor binding have yielded negative results [16,17,18,19]. This suggests that it would be more fruitful to delve into the presynaptic mechanisms underlying changes across female reproduction in central GABA synthesis and release, including glutamate decarboxylase (GAD65) and the vesicular GABA transporter, which we focus on in the present experiments
GABA concentrations in cerebrospinal fluid, and GABA release or metabolism in a number of forebrain sites, are higher in postpartum mothers compared to nonmothers and decrease when the offspring are removed [5,6,7, 49]

Summary

Introduction

The early postpartum period is associated with a number of salient behavioral modifications including elevated interest in neonates, the performance of caregiving activities, and a suppression of anxiety- and fear-related behaviors that facilitates mothers’ positive focus on the offspring [for reviews see [1, 2]]. The neurochemical underpinnings of these postpartum behaviors include numerous steroids, neuropeptides, and classical neurotransmitters [1, 3, 4]. The postpartum GABA system is acutely affected by interactions with offspring, such that cerebrospinal fluid concentrations of GABA are high when mother rats interact with pups, but drop to almost non-detectable levels within hours after the litter is removed [7]. Such changes in GABAergic activity are functionally relevant for mothers’ behavior. Experiments targeting specific forebrain sites have identified the mPFC as a locus for GABA’s involvement in both maternal caregiving and postpartum affective behaviors [8, 14, 15]

Methods

Results

Conclusion