Diabetic female rats exhibit defensive aggression during mating

Abigail Hernández-Munive, Daniela Rebolledo-Solleiro, Alonso Fernández-Guasti

DOI: https://doi.org/10.17711/SM.0185-3325.2020.005

Abstract


Introduction. Few reports have analyzed the putative association between diabetes mellitus type 1 (DM1) and aggressiveness. A previous study using a model of DM1 reported an increase in aggressive behaviors (AB) of females against the male during mating, which was prevented by insulin. However, it was unclear if such aggression was defensive or offensive.

Objective. To evaluate the different components of aggressiveness of hyperglycemic female rats in two distinct mating paradigms.

Method. DM1 was modeled in OVX Wistar rats by injecting streptozotocin (STZ) diluted in citrate buffer (50 mg/kg, i.p., for 2 consecutive days). Ten days later, female rats were treated with estradiol benzoate (10 microg, -24 hours) and progesterone (3 mg, -4 hours). A group of STZ-treated animals was administered with a long-acting insulin analogue (glargine) every 12 hours for 8 days. Aggression was recorded in non-paced mating (NPM) and paced mating (PM) paradigms. We registered: the first attack latency (FAL), the proportion of females that presented AB and its type (boxing, bites, lateral kicks and twist) and if AB were exhibited defensively or offensively.

Results. Hyperglycemic rats showed an increase in lateral kicks in NPM, whereas in PM they exhibited an increase in bites. These behaviors were always defensive and there were no changes in FAL. Insulin reduced AB.

Discussion and conclusion. Data indicate that the aggressiveness of hyperglycemic female rats is a form of defense against the proximity of the male and add information about the role of insulin on their modulation.

Keywords


Aggression; diabetes; insulin; female; rat

Full Text:

HTML Pdf ePub

References


Adams, D. B. (1979). Brain mechanisms for offense, defense, and submission. Behavioral and Brain Sciences, 2(2), 201-213. doi: 10.1017/S0140525X00061926

Akbaş, S., Karabekiroğlu, K., Ŏzgen, T., Tasdemir, G., Karakurt, M., Şenses, A., ... Aydin, M. (2009). Association between emotional and behavioral problems and metabolic control in children and adolescents with Type 1 diabetes. Journal of Endocrinological Investigation, 32(4), 325-329. doi: 10.1007/BF03345721

Aksu, I., Ates, M., Baykara, B., Kiray, M., Sisman, A. R., Buyuk, E., ... Uysal, N. (2012). Anxiety correlates to decreased blood and prefrontal cortex IGF-1 levels in streptozotocin induced diabetes. Neuroscience Letters, 531(2), 176-181. doi: 10.1016/j.neulet.2012.10.045

Andrade, M. L., Benton, D., Brain, P. F., Ramirez, J. M., & Walmsley, S. V. (1988). A reexamination of the hypoglycemia aggression hypothesis in laboratory mice. International Journal of Neuroscience, 41(3-4), 179-186. doi: 10.3109/00207458808990724

Banafshe, H. R., Hamidi, G. A., Noureddini, M., Mirhashemi, S. M., Mokhtari, R., & Shoferpour, M. (2014). Effect of curcumin on diabetic peripheral neuropathic pain: possible involvement of opioid system. European Journal of Pharmacology, 723, 202-206. doi: 10.1016/j.ejphar.2013.11.033

Banks, W. A., Owen, J. B., & Erickson, M. A. (2012). Insulin in the brain: there and back again. Pharmacology & Therapeutics, 136(1), 82-93. doi: 10.1016/j.pharmthera.2012.07.006

Benedict, C., Hallschmid, M., Hatke, A., Schultes, B., Fehm, H. L., Born, J., & Kern, W. (2004). Intranasal insulin improves memory in humans. Psychoneuroendocrinology, 29(10), 1326-1334. doi: 10.1016/j.psyneuen.2004.04.003

Bryden, K. S., Peveler, R. C., Stein, A., Neil, A., Mayou, R. A., & Dunger, D. B. (2001). Clinical and psychological course of diabetes from adolescence to young adulthood: a longitudinal cohort study. Diabetes Care, 24(9), 1536-1540. doi: 10.2337/diacare.24.9.1536

Can, O. D., Ozturk, Y., & Ozkay, U. D. (2011). Effects of insulin and St. John’s Wort treatments on anxiety, locomotory activity, depression, and active learning parameters of streptozotocin-diabetic rats. Planta Medica, 77(18), 1970-1976. doi: 10.1055/s-0031-1280129

Chakrabarty, A., Liao, Z., Mu, Y., & Smith, P. G. (2018). Inflammatory renin-angiotensin system disruption attenuates sensory hyperinnervation and mechanical hypersensitivity in a rat model of provoked vestibulodynia. The Journal of Pain, 19(3), 264-277. doi: 10.1016/j.jpain.2017.10.006

Chaouloff, F., Laude, D., Mérino, D., Serrurier, B., Baudrie, V., & Elghozi, J. L (1989). Duration of streptozotocin diabetes influences the response of hypothalamic serotonin metabolism to immobilization stress. Neuroendocrinology, 50(3), 344-350. doi: 10.1159/000125244

Cordero, M. I., Ansermet, F., & Sandi, C. (2013). Long-term programming of enhanced aggression by peripuberty stress in female rats. Psychoneuroendocrinology, 38(11), 2758-2769. doi: 10.1016/j.psyneuen.2013.07.005

Craft, S., & Stennis Watson, G. S. (2004). Insulin and neurodegenerative disease: shared and specific mechanisms. The Lancet Neurology, 3(3), 169-178. doi: 10.1016/s1474-4422(04)00681-7

da Veiga, C. P., Miczek, K. A., Lucion, A. B., & de Almeida, R. M. (2011). Social instigation and aggression in postpartum female rats: role of 5-Ht1A and 5-Ht1B receptors in the dorsal raphé nucleus and prefrontal cortex. Psychopharmacology, 213(2-3), 475-487. doi: 10.1007/s00213-010-2083-5

Efe, Y. S., & Erdem, E. (2018). A comparison of aggression and self-injury among type 1 diabetic and healthy adolescents: a sample from Turkey. Archives of Psychiatric Nursing, 32(2), 174-179. doi: 10.1016/j.apnu.2017.10.012

ElBatsh, M. M. (2015). Antidepressant-like effect of simvastatin in diabetic rats. Canadian Journal of Physiology and Pharmacology, 93(8), 649-656. doi: 10.1139/cjpp-2014-0560

Forsander, G., Bogelund, M., Haas, J., & Samuelsson, U. (2017). Adolescent life with diabetes-Gender matters for level of distress. Experiences from the national TODS study. Pediatric Diabetes, 18(7), 651-659. doi: 10.1111/pedi.12478

Gao, F., & Zheng, Z. M. (2014). Animal models of diabetic neuropathic pain. Experimental Clinical Endocrinology & Diabetes, 122(2), 100-106. doi: 10.1055/s-0033-1363234

Gonzalez, M. I., Vaziri, S., & Wilson, C. A. (1996). Behavioral effects of α-MSH and MCH after central administration in the female rat. Peptides, 17(1), 171-177. doi: 10.1016/0196-9781(95)02092-6

Gupta, D., Kurhe, Y., & Radhakrishnan, M. (2014). Antidepressant effects of insulin in streptozotocin induced diabetic mice: Modulation of brain serotonin system. Physiology & Behavior, 129, 73-78. doi: 10.1016/j.physbeh.2014.02.036

Hardy, D. F., & DeBold, J. F. (1972). Effects of coital stimulation upon behavior of the female rat. Journal of Comparative and Physiological Psychology, 78(3), 400-408. doi: 10.1037/h0032536

Hernandez-Munive, A. K., Rebolledo-Solleiro, D., Ventura-Aquino, E., & Fernandez-Guasti, A. (2018). Reduced lordosis and enhanced aggression in paced and non-paced mating in diabetic female rats. The Journal of Sexual Medicine, 15(2), 124-135. doi: 10.1016/j.jsxm.2017.11.018

Hilakivi-Clarke, L. A. (1991). Effects of tryptophan on depression and aggression in STZ-D mice. Diabetes, 40(12), 1598-1602. doi: 10.2337/diab.40.12.1598

Hood, K. K., Huestis, S., Maher, A., Butler, D., Volkening, L., & Laffel, L. M. (2006). Depressive symptoms in children and adolescents with type 1 diabetes: association with diabetes-specific characteristics. Diabetes Care, 29(6), 1389-1391. doi: 10.2337/dc06-0087

Kakleas, K., Kandyla, B., Karayianni, C., & Karavanaki, K. (2009). Psychosocial problems in adolescents with type 1 diabetes mellitus. Diabetes & Metabolism, 35(5), 339-350. doi: 10.1016/j.diabet.2009.05.002

Kim, N. N., Stankovic, M., Cushman, T. T., Goldstein, I., Munarriz, R., & Traish, A. M. (2006). Streptozotocin-induced diabetes in the rat is associated with changes in vaginal hemodynamics, morphology and biochemical markers. BMC Physiology, 6(1), 4. doi: 10.1186/1472-6793-6-4

Kleinridders, A., Ferris, H. A., Cai, W., & Kahn, C. R. (2014). Insulin action in brain regulates systemic metabolism and brain function. Diabetes, 63(7), 2232-2243. doi: 10.2337/db14-0568

Korczak, D. J., Pereira, S., Koulajian, K., Matejcek, A., & Giacca, A. (2011). Type 1 diabetes mellitus and major depressive disorder: evidence for a biological link. Diabetologia, 54(10), 2483-2493. doi: 10.1007/s00125-011-2240-3

Lašaitė, L., Dobrovolskienė, R., Danytė, E., Stankutė, I., Ražanskaitė-Virbickienė, D., Schwitzgebel, V., ... Verkauskienė, R. (2016). Diabetes distress in males and females with type 1 diabetes in adolescence and emerging adulthood. Journal of Diabetes and its Complications, 30(8), 1500-1505. doi: 10.1016/j.jdiacomp.2016.08.013

Lašaitė, L., Ostrauskas, R., Zalinkevicius, R., Jurgeviciene, N., & Radzeviciene, L. (2015). Profile of mood states in adult type 1 diabetes mellitus men and women with disease onset in childhood and in adulthood. Journal of Pediatric Endocrinology and Metabolism, 28(3-4), 279-285. doi: 10.1515/jpem-2014-0162

Leedom, L. J., Meehan, W. P., & Zeidler, A. (1987). Avoidance responding in mice with diabetes mellitus. Physiology & Behavior, 40(4), 447-451. doi:10.1016/0031-9384(87)90029-1

Leonard, B. J., Jang, Y. P., Savik, K., Plumbo, P. M., & Christensen, R. (2002). Psychosocial factors associated with levels of metabolic control in youth with type 1 diabetes. Journal of Pediatric Nursing, 17(1), 28-37. doi: 10.1053/jpdn.2002.30931

Madlafousek, J., & Hliňák, Z. (1977). Sexual behaviour of the female laboratory rat: Inventory, patterning, and measurement. Behaviour, 63(3-4), 129-174. doi: 10.1163/156853977X00397

Manjarrez-Gutierrez, G., Herrera-Marquez, R., Bueno-Santoyo, S., González-Ramírez, M., & Hernández, J. (2000). Changes in brain serotonin biosynthesis in rats with diabetes mellitus induced by streptozocin: effect of insulin treatment. Revista de Investigacion Clinica; organo del Hospital de Enfermedades de la Nutricion, 52(5), 509-516.

McDonnell, C. M., Northam, E. A., Donath, S. M., Werther, G. A., & Cameron, F. J. (2007). Hyperglycemia and externalizing behavior in children with type 1 diabetes. Diabetes Care, 30(9), 2211-2215. doi: 10.2337/dc07-0328

Meehan, W. P., Leedom, L. J., Nagayama, T., & Zeidler, A. (1987). Hyperglycemia and fight-flight behavior in nondiabetic and diabetic mice. Physiology & Behavior, 41(5), 397-403. doi: 10.1016/0031-9384(87)90072-2

Naar-King, S., Idalski, A., Ellis, D., Frey, M., Templin, T., Cunningham, P. B., & Cakan, N. (2005). Gender differences in adherence and metabolic control in urban youth with poorly controlled type 1 diabetes: the mediating role of mental health symptoms. Journal of Pediatric Psychology, 31(8), 793-802. doi: 10.1093/jpepsy/jsj090

Paredes, R. G., & Vazquez, B. (1999). What do female rats like about sex? Paced mating. Behavioural Brain Research, 105(1), 117-127. doi: 10.1016/S0166-4328(99)00087-X

Park, K., Ryu, S. B., Park, Y. I., Ahn, K., Lee, S. N., & Nam, J. H. (2001). Diabetes mellitus induces vaginal tissue fibrosis by TGF-beta 1 expression in the rat model. Journal of Sex & Marital Therapy, 27(5), 577-587. doi: 10.1080/713846811

Roy, T., & Lloyd, C. E. (2012). Epidemiology of depression and diabetes: A systematic review. Journal of Affective Disorders, 142, S8-S21. doi: 10.1016/s0165-0327(12)70004-6

Sahin, T. D., Gocmez, S. S., Eraldemir, F. C., & Utkan, T. (2019). Anxiolytic-Like and Antidepressant-Like effects of resveratrol in streptozotocin-induced diabetic rats. Noro Psikiyatr Ars, 56(2), 144-149. doi: 10.29399/npa.23176

Šerbedžija, P., & Ishii, D. N. (2012). Insulin and insulin-like growth factor prevent brain atrophy and cognitive impairment in diabetic rats. Indian Journal of Endocrinology and Metabolism, 16(Suppl 3), S601-S610. doi: 10.4103/2230-8210.105578

Takahashi A., Miczek K.A. (2013) Neurogenetics of Aggressive Behavior: Studies in Rodents. In: Miczek K., Meyer-Lindenberg A. (eds) Neuroscience of Aggression. Current Topics in Behavioral Neurosciences, 17, 3-44. Berlin, Heidelberg: Springer. doi: 10.1007/7854_2013_263

Tilov, B., Semerdzhieva, M., Bakova, D., Tornyova, B., & Stoyanov, D. (2016). Study of the relationship between aggression and chronic diseases (diabetes and hypertension). Journal of Evaluation in Clinical Practice, 22(3), 421-424. doi: 10.1111/jep.12502

Trainor, B. C., Sisk, C. L., & Nelson, R. J. (2009). Hormones and the development and expression of aggressive behavior. In Hormones, Brain and Behavior Online, 2, 167-205. Elsevier, Inc. doi: 10.1016/B978-008088783-8.00005-X

Tripathi, C. D., Mehta, A. K., & Yadav, A. M. (2016). Drug combinations in diabetic neuropathic pain: an experimental validation. Journal of Basic and Clinical Physiology and Pharmacology, 27(6), 617-624. doi: 10.1515/jbcpp-2015-0163

Umukoro, S., Aladeokin, A. C., & Eduviere, A. T. (2013). Aggressive behavior: A comprehensive review of its neurochemical mechanisms and management. Aggression and Violent Behavior, 18(2), 195-203. doi: 10.1016/j.avb.2012.11.002

van Son, J., Nyklicek, I., Pop, V. J., Blonk, M. C., Erdtsieck, R. J., Spooren, P. F., ... Pouwer, F. (2013). The effects of a mindfulness-based intervention on emotional distress, quality of life, and HbA(1c) in outpatients with diabetes (DiaMind): a randomized controlled trial. Diabetes Care, 36(4), 823-830. doi: 10.2337/dc12-1477

Vanstone, M., Rewegan, A., Brundisini, F., Dejean, D., & Giacomini, M. (2015). Patient perspectives on quality of life with uncontrolled type 1 diabetes mellitus: A systematic review and qualitative meta-synthesis. Ontario Health Technology Assessment Series, 15(17), 1-29.

Várkonyi, T., & Kempler, P. (2014). Sexual dysfunction in diabetes. Handbook of Clinical Neurology, 126, 223-232. doi: 10.1016/B978-0-444-53480-4.00017-5

Zheng, X. P., & Chen, S. H. (2013). Psycho-behavioral changes in children with type 1 diabetes mellitus. World Journal of Pediatrics, 9(3), 261-265. doi: 10.1007/s12519-013-0428-y