Autoradiographic analysis of GABAA receptor binding in the neural anxiety network of postpartum and non-postpartum laboratory rats

Abstract

Postpartum female rats exhibit a suppression of anxiety-related behaviors when compared to diestrous virgin females, pregnant females, and males. This blunted anxiety promotes optimal maternal care and involves elevated GABA neurotransmission, possibly including greater density of GABAA and benzodiazepine receptors in the postpartum brain. We here examined autoradiographic binding of [3H]muscimol to measure the total population of GABAA receptors and [3H]flunitrazepam to assess density of benzodiazepine sites in the medial prefrontal cortex, bed nucleus of the stria terminalis, amygdala, hippocampus, and periaqueductal gray of female rats sacrificed on day 7 postpartum, day 10 of pregnancy, or as diestrous virgins. A group of sexually naïve male rats was also included. We found that [3H]muscimol binding did not differ among groups in any site but that diestrous virgin females had greater [3H]flunitrazepam binding in the CA1 and dentate gyrus of the hippocampus compared to mid-pregnant females and males. Notably, postpartum and diestrous virgin females did not significantly differ in binding of either ligand in any site examined. This is the first study to evaluate the densities of GABAA and benzodiazepine binding sites simultaneously across three female reproductive states and sex with a focus on brain sites influencing anxiety-related behaviors. The results suggest that changes other GABAA receptor characteristics, such as subunit composition or increased presynaptic GABA release during interactions with offspring, must instead play a greater role in the postpartum suppression of anxiety in laboratory rats.

Use of the light–dark box to compare the anxiety-related behavior of virgin and postpartum female rats

“…Dams and diestrous virgins do not differ in GABA A or benzodiazepine receptor binding within the neural anxiety network (Miller and Lonstein, 2011), but central GABA release rises when dams interact with pups and falls when pups are removed (Qureshi et al, 1987). Some functional implications of this rise in GABA release are revealed by the increased freezing in response to an acoustic stimulus in dams treated with FG-7142 and decreased punished drinking in dams given PTZ (Hansen et al, 1985; Hansen, 1990).…”

Emotion and Mood Adaptations in the Peripartum Female: Complementary Contributions of GABA and Oxytocin

“…The cortex must not drive this change in affinity because its GABA A Rs have been reported to have decreased affinity for their ligand during late pregnancy . Brain sites contributing to the postpartum reduction in total forebrain GABA A R density are also unknown because [ 3 H]flunitrazepam and [ 3 H]muscimol binding (indicating the densities of benzodiazepine and GABA A receptor binding sites, respectively) in numerous forebrain regions involved in anxiety‐related behaviours do not differ among virgin, pregnant and early postpartum female laboratory rats .…”

Maternal Stress Induces Epigenetic Signatures of Psychiatric and Neurological Diseases in the Offspring

“…Moreover, gestational stress directly influences fetal brain development and programming of hypothalamic-pituitary-adrenal (HPA) axis function [10], [11] to induce life-long changes in stress responsiveness [12] and possibly enhanced vulnerability to psychiatric conditions, including depression and bipolar affective disorder [13]–[16] and schizophrenia [17]–[20]. The prefrontal cortex in particular is relevant to mental health disorders, which may be precipitated or exaggerated by stress, pregnancy and childbirth [21]–[23].…”