عنوان مقاله [English]
Social isolation in the early stages of life may lead to some types of neurological disorders. Dopamine is one of the most important brain neurotransmitters playing significant roles in reward pathway in the brain. The present study aimed at determining the impact of serotonin agonist and dopamine agonist on fear behavior in the rats of social isolation model. Forty rats (after the age of 23-day) were selected and kept in separate cages with black plastic buffers for six weeks. Eight rats were assigned to the control (social) group and the rest were placed in individual cages: one male rat per cage. In group 1 or control (social) group, they received saline carrier. Group 2 was only kept under social isolation conditions without any drug injections; and Group 3 received 1-(3-chloropheny) piperazine, serotonin agonist. Tolerating social isolation conditions, Group 4 received dopamine agonist apomorphine. Group 5 received both piperazine (m-cpp) serotonin agonist and dopamine agonist apomorphine. The results show that the time of entry in open arm in the group receiving apomorphine was significantly higher than in the control (social) group (P ≤ 0.001). The time of entry in open arm in the group receiving 1-(3-chlorophenyl) piperazine was significantly lower than in the control (social) group. The findings of the present study in social isolation conditions indicate that apomorphine can significantly decrease anxiety. 1-(3-chlorophenyl) piperazine (m-cpp) serotonin agonist has stimulating effects similar to serotonin, causing anxiety.
1. Ago Y., Takuma K., Matsuda T. 2014.The Potential Role of Serotonin1A Receptors in Post-weaning social isolation–Induced abnormal behaviors in rodents.Journal of Pharmacological Sciences,125(3): 237-241.
2. Ali A.A., Khalil M.G., Elariny H.A., Abu-Elfotuh K., 2017. Study on social isolation as a risk factor in development of Alzheimer's disease in rats. Brain Disorders, 6: 230-232.
3. Bauer E.P. 2015. Serotonin in fear conditioning processes. Behavioral Brain Research, 277: 68-77.
4. Bibancos T., Jardim D.L., Aneas I., Chiavegatto S. 2006. Social isolation and expression of serotonergic neurotrans mission‐related genes in several brain areas of male mice. Genes Brain Behavior, 6(6): 529-539.
5. Burghardt N.S., Bauer E.P. 2013. Acute and chronic effects of selective serotonin reuptake inhibitor treatment on fear conditioning: implications for underlying fear circuits. Neuroscience, 247(5): 253-272.
6. Chang CH, Hsiao YH., Chen YW., Yu YJ., Gean PW., 2015. Social isolation-induced increase in NMDA receptors in the hippocampus exacerbates emotional dysregulation in mice. Hippocampus, 25(4): 474-485.
9. Fischer A.G., Ullsperger M. 2017. An update on the role of serotonin and its Interplay with dopamine for Reward. Human Neuroscience, 11: 484.
10. Franklin T.B., Linder N., Russig H., Thöny B., Mansuy I.M., 2011. Influence of early stress on social abilities and serotonergic functions across generations in mice. PLoS One, 6(7): e21842.
11. Gatch M.B., 2003. Discriminative stimulus effects of m-chlorophenyl piperazine as a model of the role of serotonin receptors in anxiety. Life Sciences, 73(11): 1347-1367.
13. Ieraci A., Mallei A., Popoli M. 2016. Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice. Neural Plasticity, 1:1-13.
14. Jin Y.H., Clark A.B., Slebos R.J., Slebos R.J., Al-Refai H., Taylor J.A., Kunkel T.A., Resnick M.A., Gordenin D.A. 2003. Cadmium is a mutagen that acts by inhibiting mismatch repair. Nature Genetics, 34(3): 326-329.
15. Johnson P.L., Molosh A., Fitz S.D., Arendt D., Deehan G.A., Federici L.M., Bernabe C., Engleman E.A., Rodd Z.A., Lowry C.A., Shekhar A. 2015. Pharmacological depletion of serotonin in the basolateral amygdala complex reduces anxiety and disrupts fear conditioning., Pharmacology Biochemistry and Behavior, 138: 174-179.
16. Karkhanis A.N., Leach A.C., Yorgason J.T., Uneri A., Barth S., Niere F., Alexander N.J., Weiner J.L., McCool B.A., Raab-Graham K.F., Ferris M.J., Jones S.R. 2019. Chronic social isolation stress during peri-adolescence alters presynaptic dopamine terminaldynamics via augmentation in accumbal dopamine availability. Chemical Neuroscience, 10(4): 2033-2044.
17. Lawler C.P., Prioleau C., Lewis M.M., Mak C., Jiang D., Schetz J.A., Gonzalez A.M., Sibley D.R., Mailman R.B. 1999. Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes. Neuropsychopharmacology, 20(6): 612-627.
19. Rodriguez-Romaguera J., Stuber G.D., 2018. Social isolation co-opts fear and aggression circuits. Cell, 173(5): 1071-1072.
20. Santini Z.I., Fiori K.L., Feeney J., Tyrovolas S., Haro J.M., Koyanagi A. 2016. Social relationships, loneliness, and mental health among older men and women in Ireland: A prospective community-based study. Journal of Affective Disorders, 204: 59-69.
21. Sargin D., Oliver D.K., Lambe E.K., 2016. Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3 calcium-activated potassium channels. Elife, 5: e21416.
22. Steptoe A., Shankar A., Demakakos P., Wardle J. 2013. Social isolation, loneliness, and all-cause mortality in older men and women. Proceeding of Natlonal Academy Sciences of USA, 110(15): 5797-5801.
23. Teo A.R., Choi H Valenstein M., 2013. Social relationships and depression: ten-year follow-up from a nationally representative study. PLoS One, 8(4): e62396.
25. Zelikowsky M., Hersman S., Chawla M.K., Barnes C.A., Fanselow M.S., 2014.Neuronal ensembles in amygdala, hippocampus, and prefrontal cortex track differential components of contextual fear. Journal of Neuroscience, 34(25): 8462-8466.
26. Zlatkovic J., Todorovic N., Boskovic M., Pajovic S.B., Demajo M., Filipovic D. 2014. Different susceptibility of prefrontal cortex and hippocampus to oxidative stress following chronic social isolation stress. Molecular and Cellular Biochemistry, 393(1–2): 43-57.