Oxytocin-dopamine interactions mediate variations in maternal behavior in the rat

Abstract

Variations in maternal behavior among lactating rats associate with differences in estrogen-oxytocin interactions in the medial preoptic area (mPOA) and in dopamine levels in the nucleus accumbens (nAcc). Thus, stable, individual differences in pup licking/grooming (LG) are abolished by oxytocin receptor blockade or treatments that eliminate differences in the nAcc dopamine signal. We provide novel evidence for a direct effect of oxytocin at the level of the ventral tegmental area (VTA) in the regulation of nAcc dopamine levels. Mothers that exhibit consistently increased pup LG (i.e. high LG mothers) by comparison with low LG mothers show increased oxytocin expression in the mPOA and the paraventricular nucleus of the hypothalamus and increased projections of oxytocin-positive cells from both mPOA and paraventricular nucleus of the hypothalamus to the VTA. Direct infusion of oxytocin into the VTA increased the dopamine signal in the nAcc. Finally, high compared with low LG mothers show greater increases in dopamine signal in the nAcc during bouts of pup LG, and this difference is abolished with infusions of an oxytocin receptor antagonist directly into the VTA. These studies reveal a direct effect of oxytocin on dopamine release within the mesocorticolimbic dopamine system and are consistent with previous reports of oxytocin-dopamine interactions in the establishment and maintenance of social bonds.

Figure 1

Photomicrograph outlining the boundaries of the MPN of the mPOA used for the quantification of ICC experiments (A). Mean ± sem number of fluorogold-labeled cells in the MPN of lactating high or low LG mothers (n = 5/group) after injection in the VTA on postpartum d 6 (B). Photomicrograph depicting cells that stained positively for fluorogold (FG) (C). Mean ± sem number of MPN cells positive for oxytocin (OT) immunoreactivity in high or low LG mothers (*, P < 0.05) (D). Photomicrograph of oxytocin-positive cells in the MPN of high and low LG mothers on postpartum d 6 (E). Mean ± sem number of oxytocin- and fluorogold-positive cells in the MPN of high or low LG mothers on postpartum d 6 (*, P < 0.001) (F). Photomicrograph of single- (positive for oxytocin but not fluorogold immunoreactivity) or double-labeled (positive for both oxytocin and fluorogold immunoreactivity) cells. NOVA RED was used to visualize oxytocin immunoreactivity and DAB to visualize fluorogold immunoreactivity (G). Schematic illustration of the sites of fluorogold infusions of the five high and five low LG dams. All animals included in the analysis had confirmed infusion placement in the VTA (H).

Figure 2

Mean ± sem number of oxytocin-labeled cells (OT+) in the parvocellular and magnocellular regions of the paraventricular nucleus of the hypothalamus PVNh (A) and in the supraoptic nucleus (SON; B) of lactating high and low LG mothers on postpartum day 6 (n = 5/group/*, P < 0.05). Mean ± sem number of fluorogold (FG+)-labeled cells in the parvocellular region of the PVNh (pPVNh) of high or low LG mothers on postpartum d 6 (n = 5/group) (C). Mean ± sem number of oxytocin+/fluorogold+ double-labeled cells in the parvocellular region of the PVNh of high and low LG dams on post partum d 6 (n = 5/group, *, P < 0.05) (D). Photomicrograph outlining the magnocellular (MNCs) and parvocellular (PVCs) regions of the PVNh used for the quantification of immunocytohistochemistry experiments. NOVA RED was used to visualize oxytocin immunoreactivity and DAB to visualize fluorogold immunoreactivity (E).

Figure 3

The mean ± sem increase in dopamine (DA; nanomoles) in the nucleus accumbens shell of virgin females after the infusion of saline or oxytocin (2.4 nmol) into the VTA (n = 5/group). Infusion of oxytocin increased the dopamine (nanomoles) signal at min 2–14, 18, 22, and 24 after infusion by comparison with saline-treated animals (*, P < 0.05) (A). Mean ± sem of total area under the curve (AUC) for dopamine levels measured over the period depicted in A for virgin females infused with oxytocin or saline (*, P < 0.05) (B). Repeated-measures ANOVA was followed by a pair-wise post hoc test.

Figure 4

Mean ± sem peak increase in dopamine (DA; nanomoles) in the nAcc shell of high and low LG lactating females on postpartum d 4 or 5 after infusion with either an oxytocin antagonist (OTA) or saline in the VTA (n = 4–5/group). The saline-treated high LG mothers showed a significantly higher dopamine signal (*, P < 0.05) compared with all other groups (A). Representative recordings depicting the change in the dopamine (nanomoles) signal in the nAcc shell of high and low LG mothers before, during, and at the end of a period of pup LG on postpartum d 4/5 after infusion of an oxytocin antagonist (OTA) or saline into the VTA (red dashed line represents baseline) (B). Schematic illustration of the sites of electrochemical probe placement in the high and low LG dams included in the electrochemical and behavioral analysis. All animals included in the analysis had confirmed probe placement in the nAcc shell (n = 4–5/group) (C). Schematic illustration of the sites of cannulae placements in the high and low LG dams included in the electrochemical and behavioral analysis. All animals included in the analysis had confirmed cannulae placement in the VTAea (•, OTA; ▵, saline) (D). A two-way ANOVA was used followed by Bonferroni’s post hoc test. Figure continued on next page.

Figure 4

Mean ± sem peak increase in dopamine (DA; nanomoles) in the nAcc shell of high and low LG lactating females on postpartum d 4 or 5 after infusion with either an oxytocin antagonist (OTA) or saline in the VTA (n = 4–5/group). The saline-treated high LG mothers showed a significantly higher dopamine signal (*, P < 0.05) compared with all other groups (A). Representative recordings depicting the change in the dopamine (nanomoles) signal in the nAcc shell of high and low LG mothers before, during, and at the end of a period of pup LG on postpartum d 4/5 after infusion of an oxytocin antagonist (OTA) or saline into the VTA (red dashed line represents baseline) (B). Schematic illustration of the sites of electrochemical probe placement in the high and low LG dams included in the electrochemical and behavioral analysis. All animals included in the analysis had confirmed probe placement in the nAcc shell (n = 4–5/group) (C). Schematic illustration of the sites of cannulae placements in the high and low LG dams included in the electrochemical and behavioral analysis. All animals included in the analysis had confirmed cannulae placement in the VTAea (•, OTA; ▵, saline) (D). A two-way ANOVA was used followed by Bonferroni’s post hoc test. Figure continued on next page.