Early positive tactile stimulation reverses the increase of anxiety and decrease of sociality induced by early chronic mechanical pain in mandarin voles

Abstract

Animals may experience early negative (mechanical pain: being retrieved using an incisor by parents or attacked) or positive stimulation (being licked and groomed) that may affect emotional and social behaviors in adulthood. Whether positive tactile stimulation can reverse adverse consequences on emotional and social behaviors in adulthood resulting from chronic mechanical pain and underlying mechanisms remain unclear. This study used a tail-pinching model during development to simulate mechanical pain experienced by pups in high-social mandarin voles (Microtus mandarinus). Subsequently, brush-like positive tactile stimuli were applied to the backs of the mandarin voles. Various behavioral tests were used to measure levels of anxiety, depression, and sociability. The results showed that early tail-pinching delayed the eye opening of pups, increased levels of anxiety, reduced levels of sociality in male mandarin voles, and impaired social cognition in females during adulthood. Brushing on the back reversed some of these effects. While mandarin voles that were exposed to tail-pinching during development were exposed to sub-threshold variable stress as adults, they were more likely to show a stress-induced increase of anxiety-like behavior, reduction of sociability, and impairment of social cognition, displaying heightened susceptibility to stress, particularly in males. However, back-brushing reversed some of these effects, implying that these adults display enhanced stress resilience. In addition, tail-pinching reduced levels of serum oxytocin and increased corticosterone levels in serum, but back-brushing reversed these effects. Overall, it was found that positive tactile stimulation reversed increases in anxiety and impairments of social behavior induced by negative stimulation in male mandarin voles via alteration of oxytocin and corticosterone levels.

Keywords

emotion / mandarin vole / negative tactile stimulation / positive tactile stimulation / sociability / susceptibility

References

[1] Balikci A, Ilbay G, Ates N (2020). Neonatal tactile stimulations affect genetic generalized epilepsy and comorbid depression-like behaviors. Frontiers in Behavioral Neuroscience 14, 132.

[2] Boccia ML, Cook C, Marson L, Pedersen C (2021). Parental divorce in childhood is related to lower urinary oxytocin concentrations in adulthood. Journal of Comparative Psychology 135, 74-81.

[3] Bülbül M, Babygirija R, Cerjak D, Yoshimoto S, Ludwig K, Takahashi T (2011). Hypothalamic oxytocin attenuates CRF expression via GABA(A) receptors in rats. Brain Research 1387, 39-45.

[4] Carson DS, Berquist SW, Trujillo TH et al. (2015). Cerebrospinal fluid and plasma oxytocin concentrations are positively correlated and negatively predict anxiety in children. Molecular Psychiatry 20, 1085-1090.

[5] Cirulli F, Berry A, Alleva E (2003). Early disruption of the mother-infant relationship: Effects on brain plasticity and implications for psychopathology. Neuroscience and Biobehavioral Reviews 27, 73-82.

[6] Dallé E, Daniels WMU, Mabandla MV (2020). Long-term treatment with fluvoxamine decreases nonmotor symptoms and dopamine depletion in a postnatal stress rat model of Parkinson's disease. Oxidative Medicine and Cellular Longevity 2020, 1941480.

[7] de Kloet ER, Karst H, Joëls M (2008). Corticosteroid hormones in the central stress response: Quick-and-slow. Frontiers in Neuroendocrinology 29, 268-272.

[8] Del Giudice M, Barrett ES, Belsky J et al. (2018). Individual differences in developmental plasticity: A role for early androgens? Psychoneuroendocrinology 90, 165-173.

[9] Genovese A, Butler MG (2023). The autism spectrum: Behavioral, psychiatric and genetic associations. Genes (Basel) 14, 677.

[10] Gundlach AL, Burazin TC (1998). Galanin-galanin receptor systems in the hypothalamic paraventricular and supraoptic nuclei. Some recent findings and future challenges. Annals of the New York Academy of Sciences 863, 241-251.

[11] Guzzetta A, Baldini S, Bancale A et al. (2009). Massage accelerates brain development and the maturation of visual function. Journal of Neuroscience 29, 6042-6051.

[12] Heim C, Young LJ, Newport DJ, Mletzko T, Miller AH, Nemeroff CB (2009). Lower CSF oxytocin concentrations in women with a history of childhood abuse. Molecular Psychiatry 14, 954-958.

[13] Hou W, Huang S, Li L et al. (2023). Oxytocin treatments or activation of the paraventricular nucleus-the shell of nucleus accumbens pathway reduce adverse effects of chronic social defeat stress on emotional and social behaviors in Mandarin voles. Neuropharmacology 230, 109482.

[14] Hung LW, Neuner S, Polepalli JS et al. (2017). Gating of social reward by oxytocin in the ventral tegmental area. Science 357, 1406-1411.

[15] Imanaka A, Morinobu S, Toki S et al. (2008). Neonatal tactile stimulation reverses the effect of neonatal isolation on open-field and anxiety-like behavior, and pain sensitivity in male and female adult Sprague-Dawley rats. Behavioural Brain Research 186, 91-97.

[16] Inoue S (2022). Neural basis for estrous cycle-dependent control of female behaviors. Neuroscience Research 176, 1-8.

[17] Jaric I, Rocks D, Greally JM, Suzuki M, Kundakovic M (2019). Chromatin organization in the female mouse brain fluctuates across the oestrous cycle. Nature Communications 10, 2851.

[18] Joushi S, Esmaeilpour K, Masoumi-Ardakani Y, Esmaeili-Mahani S, Sheibani V (2021). Intranasal oxytocin administration facilitates the induction of long-term potentiation and promotes cognitive performance of maternally separated rats. Psychoneuroendocrinology 123, 105044.

[19] Juruena MF (2014). Early-life stress and HPA axis trigger recurrent adulthood depression. Epilepsy & Behavior 38, 148-159.

[20] Juruena MF, Werne Baes CV, Menezes IC, Graeff FG (2015). Early life stress in depressive patients: Role of glucocorticoid and mineralocorticoid receptors and of hypothalamic-pituitary-adrenal axis activity. Current Pharmaceutical Design 21, 1369-1378.

[21] Lai MC, Lombardo MV, Chakrabarti B et al. (2019). Neural self-representation in autistic women and association with ‘compensatory camouflaging’. Autism 23, 1210-1223.

[22] Legros JJ, Chiodera P, Geenen V (1988). Inhibitory action of exogenous oxytocin on plasma cortisol in normal human subjects: Evidence of action at the adrenal level. Neuroendocrinology 48, 204-206.

[23] Legros JJ, Chiodera P, Geenen V, Smitz S, von Frenckell R (1984). Dose-response relationship between plasma oxytocin and cortisol and adrenocorticotropin concentrations during oxytocin infusion in normal men. Journal of Clinical Endocrinology and Metabolism 58, 105-109.

[24] Li XH, Matsuura T, Xue M et al. (2021). Oxytocin in the anterior cingulate cortex attenuates neuropathic pain and emotional anxiety by inhibiting presynaptic long-term potentiation. Cell Reports 36, 109411.

[25] Liu B, Qiao L, Liu K, Liu J, Piccinni-Ash TJ, Chen ZF (2022a). Molecular and neural basis of pleasant touch sensation. Science 376, 483-491.

[26] Liu Y, Deng SL, Li LX et al. (2022b). A circuit from dorsal hippocampal CA3 to parvafox nucleus mediates chronic social defeat stress-induced deficits in preference for social novelty. Science Advances 8, eabe8828.

[27] Marsh N, Marsh AA, Lee MR, Hurlemann R (2021). Oxytocin and the neurobiology of prosocial behavior. The Neuroscientist 27, 604-619.

[28] McGlone F, Wessberg J, Olausson H (2014). Discriminative and affective touch: Sensing and feeling. Neuron 82, 737-755.

[29] McPherson RJ, Gleason C, Mascher-Denen M, Chan M, Kellert B, Juul SE (2007). A new model of neonatal stress which produces lasting neurobehavioral effects in adult rats. Neonatology 92, 33-41.

[30] Moberg KU, Handlin L, Petersson M (2020). Neuroendocrine mechanisms involved in the physiological effects caused by skin-to-skin contact—With a particular focus on the oxytocinergic system. Infant Behavior and Development 61, 101482.

[31] Moisan MP (2021). Sexual dimorphism in glucocorticoid stress response. International Journal of Molecular Sciences 22, 3139.

[32] Mooney-Leber SM, Brummelte S (2020). Neonatal pain and reduced maternal care alter adult behavior and hypothalamic-pituitary-adrenal axis reactivity in a sex-specific manner. Developmental Psychobiology 62, 631-643.

[33] Mooney-Leber SM, Spielmann SS, Brummelte S (2018). Repetitive neonatal pain and reduced maternal care alter brain neurochemistry. Developmental Psychobiology 60, 963-974.

[34] Moraitis AG, Block T, Nguyen D, Belanoff JK (2017). The role of glucocorticoid receptors in metabolic syndrome and psychiatric illness. Journal of Steroid Biochemistry and Molecular Biology 165, 114-120.

[35] Okabe S, Yoshida M, Takayanagi Y, Onaka T (2015). Activation of hypothalamic oxytocin neurons following tactile stimuli in rats. Neuroscience Letters 600, 22-27.

[36] Opacka-Juffry J, Mohiyeddini C (2012). Experience of stress in childhood negatively correlates with plasma oxytocin concentration in adult men. Stress (Amsterdam, Netherlands) 15, 1-10.

[37] Opendak M, Sullivan RM (2019). Unique infant neurobiology produces distinctive trauma processing. Developmental Cognitive Neuroscience 36, 100637.

[38] Parker KJ, Maestripieri D (2011). Identifying key features of early stressful experiences that produce stress vulnerability and resilience in primates. Neuroscience and Biobehavioral Reviews 35, 1466-1483.

[39] Peng B, Xu Q, Liu J, Guo S, Borgland SL, Liu S (2021). Corticosterone attenuates reward-seeking behavior and increases anxiety via D2 receptor signaling in ventral tegmental area dopamine neurons. Journal of Neuroscience 41, 1566-1581.

[40] Peña CJ, Smith M, Ramakrishnan A et al. (2019). Early life stress alters transcriptomic patterning across reward circuitry in male and female mice. Nature Communications 10, 5098.

[41] Raineki C, Opendak M, Sarro E et al. (2019). During infant maltreatment, stress targets hippocampus, but stress with mother present targets amygdala and social behavior. PNAS 116, 22821-22832.

[42] Richards S, Mychasiuk R, Kolb B, Gibb R (2012). Tactile stimulation during development alters behaviour and neuroanatomical organization of normal rats. Behavioural Brain Research 231, 86-91.

[43] Roversi K, Buizza C, Brivio P et al. (2020). Neonatal tactile stimulation alters behaviors in heterozygous serotonin transporter male rats: Role of the amygdala. Frontiers in Behavioral Neuroscience 14, 142.

[44] Salberg S, Sgro M, Brady RD, Noel M, Mychasiuk R (2020). The development of adolescent chronic pain following traumatic brain injury and surgery: The role of diet and early life stress. Developmental Neuroscience 42, 2-11.

[45] Santarelli S, Zimmermann C, Kalideris G et al. (2017). An adverse early life environment can enhance stress resilience in adulthood. Psychoneuroendocrinology 78, 213-221.

[46] Scatliffe N, Casavant S, Vittner D, Cong X (2019). Oxytocin and early parent-infant interactions: A systematic review. International Journal of Nursing Sciences 6, 445-453.

[47] Schanberg SM, Field TM (1987). Sensory deprivation stress and supplemental stimulation in the rat pup and preterm human neonate. Child Development 58, 1431-1447.

[48] Shi DD, Zhang YD, Ren YY, Peng SY, Yuan TF, Wang Z (2021). Predictable maternal separation confers adult stress resilience via the medial prefrontal cortex oxytocin signaling pathway in rats. Molecular Psychiatry 26, 7296-7307.

[49] Suri D, Teixeira CM, Cagliostro MK, Mahadevia D, Ansorge MS (2015). Monoamine-sensitive developmental periods impacting adult emotional and cognitive behaviors. Neuropsychopharmacology 40, 88-112.

[50] Takahashi T (2020). Sensory stimulation of oxytocin release is associated with stress management and maternal care. Frontiers in Psychology 11, 588068.

[51] Uvnäs-Moberg K, Gross MM, Calleja-Agius J, Turner JD (2024). The Yin and Yang of the oxytocin and stress systems: Opposites, yet interdependent and intertwined determinants of lifelong health trajectories. Frontiers in Endocrinology 15, 1272270.

[52] Uvnäs-Moberg K, Handlin L, Petersson M (2014). Self-soothing behaviors with particular reference to oxytocin release induced by non-noxious sensory stimulation. Frontiers in Psychology 5, 1529.

[53] Vella ET, Evans CC, Williams S, Wynne-Edwards KE (2004). Neonatal anesthesia for studies of hamster parental behavior when infanticidal aggression is a possibility. Comparative Medicine 54, 202-208.

[54] Vittner D, McGrath J, Robinson J et al. (2018). Increase in oxytocin from skin-to-skin contact enhances development of parent-infant relationship. Biological Research for Nursing 20, 54-62.

[55] Wismer Fries AB, Ziegler TE, Kurian JR, Jacoris S, Pollak SD (2005). Early experience in humans is associated with changes in neuropeptides critical for regulating social behavior. PNAS 102, 17237-17240.

[56] Wong C, Barkai O, Wang F et al. (2022). mTORC2 mediates structural plasticity in distal nociceptive endings that contributes to pain hypersensitivity following inflammation. Journal of Clinical Investigation 132, e152635.

[57] Zhang Y, Cao SX, Sun P et al. (2016). Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus. Cell Research 26, 728-742.

[58] Zuloaga DG, Heck AL, De Guzman RM, Handa RJ (2020). Roles for androgens in mediating the sex differences of neuroendocrine and behavioral stress responses. Biology of Sex Differences 11, 44.

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