Table 2.

OT Effect on Instinctive Behavior and the Underlying Mechanisms.

Category	Physiologic effects	Neural mechanisms	Pharmacological effects	References
Eating and drinking	(1) Decrease food and drinking intake driven by energy; block consumption of toxic food and increase proactive control over feeding with overweight.	(2) Activate VMH and DVC; change activity of the LH and AN; block alcohol-induced DA release within the NAc; activate paraventricular thalamic neurons and suppress HPA axis.	(3) Improve feeding and social skills of infants with Prader-Willi syndrome; improves feeding of patients with anorexia nervosa and inhibit MCH neuronal activity in the LH.	(1) (Bowen et al., 2011; Gartner et al., 2018; Klockars et al., 2017; Pirnia et al., 2020; Plessow et al., 2021); (2) (Althammer & Grinevich, 2017; Klockars et al., 2017; McConn et al., 2019b; Peters et al., 2017; Yao et al., 2012); (3) (Russell et al., 2018; Tauber et al., 2017)
Reproduction	(4) Promote sex processes; stimulate HPG axis activity and ovulation; maintain normal menstruation and pregnancy; determine pulsatile OT release during parturition and breastfeeding and maternal behavior.	(5) Activate OT-DAergic neural pathways; increase GnRH release; activate PVN-VTA/SEG pathways; promote maturation of pulsatile OT release machinery involving the SON, PVN and MB as well as OT neurons-maternal behavior-regulating brain regions.	(6) Improve sexuality and its quality; accelerate parturition; facilitate conditional milk letdown; improve erectile dysfunction in aged people with Parkinson's disease; alleviate menstrual migraine and postpartum mood disorders.	(4) (Cera et al., 2021; Dekker et al., 2021; Evans et al., 2003; Higuchi & Okere, 2002); (5) (Bealer et al., 2010; Hou et al., 2016; Li et al., 2021d; Selvage & Johnston, 2004; Uta et al., 2021; Wang et al., 2013); (6) (Bealer et al., 2010; Bharadwaj et al., 2021; Cowley, 2005; Lassey et al., 2021; Sakakibara et al., 2010)
Anti-aging	(7) Reduction of OT secretion is accompanied with reduced general health levels, immunity, sexuality and cognitive activity.	(8) Reduced number of OT neurons makes all OT-associated brain functions decrease over time.	(9) Increase functional connectivity of neural circuits involved in social perception; improve emotional stability and body functions	(7) (Maestrini et al., 2018; Orihashi et al., 2020); (8) (Sannino et al., 2017; Zohrabi et al., 2020); (9) (Crowley et al., 2015; Sakakibara et al., 2010; Valdes-Hernandeza et al., 2021; Wang et al., 2019b).
Nociception and analgesia	(10) OTR SNP increases pain; OT inhibits chronic somatic pains and visceral pain while reducing panic emotions to injury.	(11) Increase neural activity and neural connections between different brain areas; increase GABAergic signals in the brain and NA signals in spinal cord.	(12) Improve chronic pelvic and low back pains; inhibit the DRG, ACC, PAG, amygdala and NAc regions; increase social proximity and support and anxiolysis.	(10) (Lucas et al., 2021; Tsushima et al., 2021); (11) (Gamal-Eltrabily et al., 2020; Schneider et al., 2020; Yang et al., 2011; Zhu et al., 2021); (12) (Flynn et al., 2021; Kreuder et al., 2019; Riem et al., 2021).
Sleep	(13) Improve sleep quality in postpartum women, cancer survivors, patients with ALS and women with a history of sexual assault.	(14) Inhibit HPA axis and melatonin secretion; cause anxiolytic, anti-depression, sedating effects and emotional stability; regulate MB activity.	(15) Increase respiratory rate and reduce obstructive event duration and oxygen desaturation in patients with sleep apnea.	(13) (Comasco et al., 2016; Gabery et al., 2021; Kendall-Tackett et al., 2013; Lipschitz et al., 2015); (14) (Comasco et al., 2016; Bulbul et al., 2011; Teclemariam-Mesbah et al., 1997; (15) (Jain et al., 2017; Jain et al., 2020).

Abbreviations: ACC, anterior cingulate cortex; ALS, amyotrophic lateral sclerosis;AN, arcuate nucleus; DA, dopamine; DRG, dorsal root ganglion; DVC, dorsal vagal complex; GABA, ɣ-aminobutyric acid; GnRH, gonadotropin-releasing hormone; HPA axis, hypothalamic-pituitary-adrenal axis; HPG, hypothalamic-pituitary-gonadal axis; LH, lateral hypothalamus; MCH, melanin-concentrating hormone; MB, mammillary body complex; NA, norepinephrine; NAc, nucleus accumbens; OT, oxytocin; OTR, OT receptor; PAG, Periaqueductal gray; PVN, paraventricular nucleus; SEG, Spinal ejaculation generator; SNP, single nucleotide polymorphism; SON, supraoptic nucleus; VMH, Ventromedial hypothalamic nucleus; VP, vasopressin; VTA, ventral tegmental area.