Maternal Separation Model of Postpartum Depression: Potential Role for Nucleus Accumbens Dopamine D1-D2 Receptor Heteromer

Neurochem Res. 2020 Dec;45(12):2978-2990. doi: 10.1007/s11064-020-03145-5. Epub 2020 Oct 15.

Abstract

Postpartum depression is a mood disorder with a distinct neurobiological and behavioural profile occurring during and after the postpartum period. Dopamine pathways in the limbic regions of the brain such as the nucleus accumbens (NAc) have been shown to be involved in the etiology of depressive disorders. Selective activation of the dopamine D1-D2 receptor heteromer has been demonsrated to cause depressive- and anxiogenic-like behaviours in rats. The maternal separation model involving three hour daily maternal separation (MS) from pups on PPD 2-15 on anxiety-, depression- and anhedonia-like behaviors in the dams was investigated, together with plasma corticosterone, oxytocin and D1-D2 heteromer expression in the NAc core and shell in non-MS and MS dams. Depression, anxiety and anhedonia-like behaviours were measured using the forced swim test, elevated plus maze and sucrose preference test, respectively. In comparison to non-MS controls, MS dams displayed slightly higher depressive and anxiety-like behaviours with no difference in anhedonia-like behaviours. The MS dams displayed significantly increased care of pups after their retrieval with higher bouts of nursing, lower latency to nurse, lower bouts of out nest behaviour and decreased self-care. There was no significant alteration in D1-D2 heteromer expression in NAc core and shell between mothers of either group (MS, non-MS) or between postpartum rats and nonpregnant female rats, remaining higher than in male rats. This data provides evidence for the maternal separation model in producing a postpartum depression-like profile, but with maternal resilience able to modify behaviours to counteract any potential deleterious consequences to the pups.

Keywords: Calcium; Depression; Dopamine; Dopamine receptors; GPCR; Heteromer; Post partum depression; Receptor oligomer.

MeSH terms

  • Animals
  • Anxiety / metabolism
  • Corticosterone / metabolism
  • Depression / metabolism
  • Depression, Postpartum / metabolism*
  • Female
  • Male
  • Maternal Behavior
  • Maternal Deprivation
  • Nucleus Accumbens / metabolism*
  • Oxytocin / metabolism
  • Pregnancy
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / metabolism*
  • Receptors, Dopamine D2 / metabolism*

Substances

  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Oxytocin
  • Corticosterone