Postpartum scarcity-adversity disrupts maternal behavior and induces a hypodopaminergic state in the rat dam and adult female offspring

Abstract

Postpartum adversity is among the strongest predictors for the emergence of postpartum depression (PPD) in humans and a translational risk factor employed in rodent models. Parental care is disturbed under conditions of environmental adversity, including low resource environments, and in PPD. Nonetheless, the neural changes associated with these adversity-induced maladaptive behavioral states remain poorly understood. Postpartum scarcity-adversity can be modeled in rats by providing the dam with limited bedding and nesting (LBN) materials, which mimics the effects of a stressful low resource environment in potentiating maltreatment/neglect in humans. Indeed, LBN exposure from postpartum days (PD) 2-9 increased adverse maternal behaviors, impaired pup retrieval, and increased passive stress coping responses. Since mesolimbic dopamine (DA) activity is an important mechanism for motivated maternal behavior and is implicated in PPD, we assessed the impact of postpartum scarcity-adversity on in vivo electrophysiological properties of ventral tegmental area (VTA) DA neurons at two timepoints. We found reduced numbers of active VTA DA neurons in LBN dams at PD 9-10 but not PD-21, suggesting a transient impact on VTA population activity in LBN dams. Finally, we assessed the impact of early life scarcity-adversity on VTA DA function by conducting VTA recordings in adult female offspring and found a long-lasting attenuation in DA activity. These findings highlight a link between adversity-induced deficits in DA function and disrupted maternal behavior, suggesting the VTA/mesolimbic DA system as a potential mechanism by which postpartum scarcity-adversity drives aberrant maternal behavior, and early postnatal programming of adult VTA function in the offspring.

Fig. 1. Schematic depiction of the timeline and experimental design.

A Dams gave birth (PD 0) and were assigned to control (CON) or postpartum scarcity-adversity (LBN) conditions from PD 2–9. Home cage observations were conducted 3× per day, daily from PD 2–6 during both light/dark cycle periods. Dams underwent electrophysiological recordings of the VTA during the last days of LBN (PD 9–10) using an acute, terminal procedure. A separate cohort of dams underwent LBN from PD 2–9 and VTA recordings at PD 20–21 to test for duration of effects. B A separate cohort of dams were housed in a CON or LBN cage from PD 2–9 and were tested for pup retrieval at PD7 and in the FST at PD 9. LBN was ended on the afternoon of PD 9 and dams were kept in normal bedding conditions until weaning of pups. A subset of female pups was kept for assessing long-term effects of early postnatal scarcity-adversity in the adult offspring. C Female pups were born and reared with a CON or LBN mother from PD 2–9 and weaned at PD 21. Rats were kept in pairs and undisturbed (except for weekly animal care) until they reached adulthood, at which point they were used for VTA DA neuron recordings. PD postpartum day, CON control, LBN limited bedding and nesting, VTA ventral tegmental area, FST forced swim test, DA dopamine.

Fig. 2. LBN exposure increases negative maternal behaviors directed at pups and produces a fragmented nest environment.

During the light cycle observation sessions, LBN dams exhibited increased percentages of A stepping (p = 0.0017), B dragging (p = 0.0011), C transporting pups (p = 0.0006), and D shoving pups away (p = 0.0023) (n = 7/group). LBN dams also spent more time nest-building (p = 0.0096) and with scattered litter (p = 0.0029). LBN dams also spent greater percentages of time G stepping pups (p = 0.0006), H dragging pups (p = 0.0028), I transporting pups (p = 0.0006), J pushing or shoving pups away (p = 0.04), K nest-building (p = 0.0012) and L with a scattered litter (p = 0.04) during nighttime observation sessions (n = 7/group). Error bars represent mean ± SEM. Gray bars represent control dams (CON), pink bars represent dams that underwent scarcity-adversity (LBN). *p < 0.05, **p < 0.01, ***p < 0.001.

Fig. 3. Postpartum scarcity-adversity impairs pup retrieval and enhances passive FST coping.

A Compared to controls, LBN dams exhibited longer latencies to retrieve pups (Mann–Whitney: U = 8, p = 0.01) at PD 7 (n = 7–9/group). B When tested in the FST at PD 9, these same dams (i.e., LBN) also exhibited increased immobility duration compared to CON (t-test: t₁₄ = 2.684, p = 0.02; n = 7–9/group), suggesting an enhanced passive coping response induced by postpartum adversity. Error bars represent mean ± SEM. *p < 0.05.

Fig. 4. Postpartum scarcity-adversity induces a time-dependent attenuation in VTA population activity.

A VTA DA neuron sampling: population activity was assessed by passing the electrode trough the VTA in a predetermined grid pattern (3 × 3) of 9 tracks separated by 0.2 mm. B A representative dopaminergic neuron waveform. C At PD 9–10, LBN dams exhibited attenuated VTA population activity, as indexed by a reduction in the number of spontaneously active DA neurons found, compared to CON dams (t-test: p = 0.0006, n = 5/group). D No effect of LBN on DA neuron firing rate (p = 0.85) at PD 9–10. E No effect of LBN was found for percentage of spikes firing in burst (p = 0.87) at PD-9–10. F When assessed at PD 20–21, no differences in VTA population were found between CON and LBN dams for VTA population activity (p = 0.54; n = 5/group). G At PD 20–21, LBN and CON dams exhibited comparable DA neuron firing rate (p = 0.34). H No difference between LBN and CON dams in percentage of spikes firing in burst (p = 0.97) at PD 20–21. Error bars represent mean ± SEM. ***p < 0.001.

Fig. 5. Long-lasting effects of LBN exposure on VTA DA neuron activity in adult female offspring.

A Adult female rats that were reared under early life scarcity-adversity conditions (i.e., LBN dam PD 2–9) had a reduced number of active VA DA neurons compared to adult female rats reared with CON dams (Mann–Whitney: U = 4.5, p = 0.0022; n = 8/group). B Adult female rats reared with LBN dams exhibited increased basal DA neuron firing rate (U = 486, p = 0.0091). C No difference between CON and LBN offspring in percentage of spikes firing in burst (p = 0.08). Error bars represent mean ± SEM. **p < 0.01.