Oxytocin interactions with central dopamine and serotonin systems regulate different components of motherhood

Abstract

The role of oxytocin in maternal caregiving and other postpartum behaviours has been studied for more than five decades. How oxytocin interacts with other neurochemical systems to enact these behavioural changes, however, is only slowly being elucidated. The best-studied oxytocin-neurotransmitter interaction is with the mesolimbic dopamine system, and this interaction is essential for maternal motivation and active caregiving behaviours such as retrieval of pups. Considerably less attention has been dedicated to investigating how oxytocin interacts with central serotonin to influence postpartum behaviour. Recently, it has become clear that while oxytocin-dopamine interactions regulate the motivational and pup-approach aspects of maternal caregiving behaviours, oxytocin-serotonin interactions appear to regulate nearly all other aspects including postpartum nursing, aggression, anxiety-like behaviour and stress coping strategy. Collectively, oxytocin's interactions with central dopamine and serotonin systems are thus critical for the entire suite of behavioural adaptations exhibited in the postpartum period, and these sites of interaction are potential pharmacological targets for where oxytocin could help to ameliorate deficits in maternal caregiving and poor postpartum mental health. This article is part of the theme issue 'Interplays between oxytocin and other neuromodulators in shaping complex social behaviours'.

Keywords: dopamine; dorsal raphe; oxytocin; serotonin; ventral tegmental area.

Figure 1.

Oxytocin receptor antagonism in the ventral tegmental area or medial preoptic area impairs maternal retrieval. Latency (mean ± SEM) taken by postpartum rats to retrieve four, six or eight pups after bilateral infusions of (top) the oxytocin receptor antagonist PPT (2.0 µg total), a specific V₁ receptor antagonist (2.0 µg total) or saline bilaterally into the VTA, or (bottom) the specific oxytocin receptor antagonist OTA (0.50 µg total), the V₁ receptor antagonist (2.0 µg total) or saline into the mPOA. PPT, [Pen¹,Phe²Thr⁴delta^3,4,Pro⁷,Orn⁸]-oxytocin; V₁ antagonist, [d(CH2)^1,5,O-Me-Tyr²,Arg⁸]-vasopressin; OTA, [d(CH²)^1,5|,0-Me-Try², Thr⁴Tyr⁹,Orn⁸]-vasotocin. Figure modified from Pedersen et al. [68].

Figure 2.

Oxytocin administration into the ventral tegmental area increases dopamine release in the nucleus accumbens. Dopamine levels (mean ± SEM area under the curve) in the nucleus accumbens shell of virgin females after VTA infusion of saline or 2.4 nmol oxytocin. Asterisk indicates significant difference between groups at the individual time points, p < 0.05. Figure modified from Shahrokh et al. [72].

Figure 3.

Oxytocin receptor expression in the dorsal raphe across female reproduction. (a) Representative brain atlas highlighting the dorsal raphe (DR) region of interest (small black box) and autoradiographs of oxytocin receptor (OTR) binding in the DR of representative dioestrus virgin (DV), pregnancy day 10 (Preg 10), recently parturient (Part), and postpartum day 7 (PPD7) female rats. (b) OTR binding in the DR and (c) across level of the DR of females sacrificed as DV, on Preg 10, Part, or on PPD7. (d,e) Representative photomicrographs of OTR/tryptophan hydroxylase (TPH) dual-label immunofluorescence in the DR. Yellow, magenta and blue arrows indicate dual-labelled OTR/TPH, OTR-only, and TPH-only immunofluorescence, respectively. All data presented as means ± SEMs. Scale bars: (a) = 2 mm, (d) = 100 μm, (e) = 10 µm. aq, cerebral aqueduct. Reproduced from Grieb & Lonstein [146].

Figure 4.

Experimental timeline and validation of oxytocin receptor knockdown. (a) Experimental timeline. (b) Validation of viral construct in vivo showing oxytocin receptor (OTR) expression in the DR of scrambled-vector treated (Scrambled) and shRNA-vector treated (OTRKD) recently parturient rats. (c) Representative photomicrograph and brain atlas diagram showing the extent of viral vector infection in the DR. All data presented as means ± SEMs. Asterisk indicates significant difference between groups, p < 0.05. Scale bar in c = 1 mm. Reproduced from Grieb et al. [147].

Figure 5.

Effects of oxytocin receptor knockdown in the dorsal raphe on maternal caregiving. (a) Percentage of dams with pup loss after scrambled-vector treatment (Scrambled) or shRNA-vector treatment (OTRKD). (b) Frequency that dams were in the nest, (c) nursing in any posture, (d) nursing specifically in a kyphotic posture, (e) showing non-pup directed behaviour and (f) perioral activity by Scrambled and OTRKD dams. All data are presented as means ± SEMs. Asterisk indicates significant differences between groups, p < 0.05. Reproduced from Grieb et al. [147].

Figure 6.

Effects of oxytocin receptor knockdown in the dorsal raphe on maternal affective behaviours. (a) Frequency of attacks by scrambled-vector treated (Scrambled) and shRNA-vector treated (OTRKD) dams. (b) Total duration of attacks and (c) latency to attack by Scrambled and OTRKD dams. (d) Percentage of time spent in the open arms of an elevated plus maze and (e) floating in the forced swim test by Scrambled and OTRKD dams. All data presented as means ± SEMs. Asterisk indicates significant differences between groups, p < 0.05. Reproduced from Grieb & Lonstein [146].