Dopamine downregulation in novel rodent models useful for the study of postpartum depression

Abstract

Postpartum depression (PPD) is the most common psychiatric disorder following childbirth and is characterized by maternal mood disturbances, impaired maternal responses, and disrupted caregiving- all of which negatively impact offspring development. Since PPD has detrimental consequences for both mother and child, clinical and preclinical research has focused on identifying brain changes associated with this disorder. In humans, PPD is linked to dysregulated mesolimbic dopamine (DA) system function and altered neural responses (i.e., decreased reward-related activity) to infant-related cues, which are considered hallmark features of PPD. In accordance, rodent models employing translational risk factors useful for the study of PPD have demonstrated alterations in mesolimbic DA system structure and function, and these changes are reviewed here. We also present two novel rodent models based on postpartum adversity exposure (i.e., pup removal, scarcity-adversity) which result in PPD-relevant behavioral changes (e.g., disrupted mother-infant interactions, deficits in maternal behavior, depressive-like phenotypes) and attenuated ventral tegmental area (VTA) DA neuron activity consistent with a hypodopaminergic state. Furthermore, we highlight open questions and future directions for these rodent models. In sum, human and rodent studies converge in showing blunted mesolimbic DA function (i.e., DA downregulation) in PPD. We propose that reduced activity of VTA DA neurons, resulting in downregulation of the mesolimbic DA system, interferes with reward-related processes necessary for maternal motivation and responsiveness. Thus, the mesolimbic DA system may constitute a therapeutic target for ameliorating reward-related deficits in PPD.

Neurosteroid Modulation of Synaptic and Extrasynaptic GABAA Receptors of the Mouse Nucleus Accumbens

“…This pathway comprises an important component of the reward system and is implicated in disrupted mood and anhedonia, both of which are integral components of depressive disturbances [12][13][14]. Importantly, changes in the activity of this pathway are implicated in PPD [15,16].…”

“…The ventral tegmental area is a key hub sending dopaminergic innervation to the prefrontal cortex, amygdala, and the nucleus accumbens. These dopaminergic projections are implicated in maternal behaviours associated with reward and motivation for both rodents and humans [15]. Furthermore, human brain imaging studies report that those with PPD exhibit reduced activation of these VTA-driven pathways in response to reward and to infant offspring engagement [15,16].…”

Effects of reproductive experience on cost-benefit decision making in female rats

“…Previous work with the RDT shows that higher levels of risk taking are associated with both higher levels of evoked dopamine release in nucleus accumbens ( Freels et al, 2020 ) and lower expression of D2 receptor mRNA in striatum ( Mitchell et al, 2014 ). Dopamine signaling is also implicated in some aspects of reproduction-related behavior, including food cravings during pregnancy, maternal behavior, and post-partum depression ( Robinson et al, 2011 ; Rincón-Cortés and Grace, 2020 , 2022 ; Haddad-Tóvolli et al, 2022 ). Recordings of dopamine availability from nucleus accumbens in rats using fast-scan cyclic voltammetry show dopamine transients in mothers when interacting with pups, and that evoked dopamine release under anesthesia is greater in early post-partum compared to reproductively-naïve rats ( Robinson et al, 2011 ; Shnitko et al, 2017 ).…”

Effects of Reproductive Experience on Cost-Benefit Decision Making in Females and Males

“…Previous work with the RDT shows that higher levels of risk taking are associated with both higher levels of evoked dopamine release in nucleus accumbens (Freels et al, 2020) and lower expression of D2 receptor mRNA in striatum (Mitchell et al, 2014). Dopamine signaling is also implicated in some aspects of reproduction-related behavior, including food cravings during pregnancy, maternal behavior, and post-partum depression (Haddad-Tóvolli et al, 2022; Rincón-Cortés & Grace, 2020; 2022; Robinson et al, 2011). Recordings of dopamine availability from nucleus accumbens in rats using fast-scan cyclic voltammetry show dopamine transients in mothers when interacting with pups, and that evoked dopamine release under anesthesia is greater in post-partum compared to reproductively naïve rats (Robinson et al, 2011; Shnitko et al, 2017).…”