Maternal caregiving is a dynamic process that requires extensive cognitive, motivational, and affective processing. World-wide, approximately 17% of mothers are diagnosed with postpartum depression yearly (Wang et al., 2021). Untreated, mothers with postpartum depression experience deficits in cognition, motivation, affect, and parenting (Arteche et al., 2011; Dix and Meunier, 2009; Lovejoy et al., 2000). Although postpartum depression is related to compromised parenting, to date, few studies have examined the neurobiological mechanisms by which maternal behavior is compromised in postpartum depression (Field, 2010; Murray et al., 1996). This dissertation aims to examine how depression neurobiologically disrupts parenting abilities. These studies utilize the Wistar-Kyoto (WKY) animal model of depression and control Sprague-Dawley (SD) rats, which differ dramatically in their cognitive, motivational, affective, and parenting abilities. Through behavioral, hormonal, neurochemical, and neurogenetic analyses this body of work identified that depression-related caregiving deficits of WKY mothers are associated with substantial dysfunction of mesocorticolimbic brain circuitry. Findings from these experiments provide a new perspective on how cognitive and motivational components of caregiving behavior may be neurobiologically disrupted in mothers with depression.