Besides deficits in social communication and interaction, repetitive behavior patterns are core manifestations of autism spectrum disorder (ASD). Phenotypes are heterogeneous and can range from simple lower-order motor stereotypies to more complex higher-order cognitive inflexibility and fixated interests. Due to ASD's multifaceted etiology, animal models are often generated from monogenic diseases associated with ASD, such as Tuberous Sclerosis Complex (TSC), and are expected to copy behavioral core deficits to increase the model´s translational value for ASD disease research and novel treatment development. The global haploinsufficient Tsc2+/- Eker rat model has been shown to display ASD core symptoms in the social domain. However, the presence and extent of aberrant repetitive behavior patterns in the Eker rat remain to be investigated. Thus, the present study applied a set of behavioral tests to determine the repetitive behavioral profile in Tsc2+/- Eker rats and used brain-region-specific neurotransmitter analysis to support findings on a molecular level. Tsc2+/- animals demonstrated lower-order repetitive behavior in the form of excessive self-grooming and nestlet shredding under non-stressful conditions that co-occurred alongside social interaction deficits. However, no higher-order repetitive behavior was detected in Tsc2+/- rats. Interestingly, Tsc2+/- rats exhibited increased levels of homeostatic dopamine in the prefrontal cortex, supporting the link between aberrant cortical dopaminergic transmission and the appearance of lower-order repetitive phenotypes. Together, our results support the Tsc2+/- Eker rat as a model of ASD-like behavior for further investigation of ASD-related development and neurobiology.

Department of Child and Adolescent Psychiatry University Medical Center Göttingen Germany

Department of Psychiatry and Psychotherapy University Hospital Carl Gustav Carus Technische Universität Dresden Dresden Germany

National Institute of Mental Health Klecany Czechia

Ruhr University Bochum Bochum Germany

Zobrazit více v PubMed

American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5. 5th ed. Arlington: American Psychiatric Association; 2013.

Christensen DL, Bilder DA, Zahorodny W, Pettygrove S, Durkin MS, Fitzgerald RT, et al. Prevalence and characteristics of autism spectrum disorder among 4-year-old children in the autism and developmental disabilities monitoring network. J Dev Behav Pediatr. 2016;37(1):1–8. PubMed DOI

Zeidan J, Fombonne E, Scorah J, Ibrahim A, Durkin MS, Saxena S, et al. Global prevalence of autism: a systematic review update. Autism Res. 2022;15(5):778–90. PubMed DOI PMC

McCracken JT, Anagnostou E, Arango C, Dawson G, Farchione T, Mantua V, et al. Drug development for autism spectrum disorder (ASD): progress, challenges, and future directions. Eur Neuropsychopharmacol. 2021;48:3–31. PubMed DOI PMC

Gogate A, Kaur K, Khalil R, Bashtawi M, Morris MA, Goodspeed K, et al. The genetic landscape of autism spectrum disorder in an ancestrally diverse cohort. Npj Genom Med. 2024;9(1):1–22. PubMed PMC

Willsey HR, Willsey AJ, Wang B, State MW. Genomics, convergent neuroscience and progress in understanding autism spectrum disorder. Nat Rev Neurosci. 2022;23(6):323–41. PubMed DOI PMC

Satterstrom FK, Kosmicki JA, Wang J, Breen MS, De Rubeis S, An JY, et al. Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism. Cell. 2020;180(3):568–e58423. PubMed DOI PMC

Gaugler T, Klei L, Sanders SJ, Bodea CA, Goldberg AP, Lee AB, et al. Most genetic risk for autism resides with common variation. Nat Genet. 2014;46(8):881–5. PubMed DOI PMC

Geschwind DH. Genetics of autism spectrum disorders. Trends Cogn Sci. 2011;15(9):409–16. PubMed DOI PMC

Kazdoba TM, Leach PT, Crawley JN. Behavioral phenotypes of genetic mouse models of autism. Genes Brain Behav. 2016;15(1):7–26. PubMed DOI PMC

Möhrle D, Fernández M, Peñagarikano O, Frick A, Allman B, Schmid S. What we can learn from a genetic rodent model about autism. Neurosci Biobehavioral Reviews. 2020;109:29–53. PubMed DOI

Kas MJ, Glennon JC, Buitelaar J, Ey E, Biemans B, Crawley J, et al. Assessing behavioural and cognitive domains of autism spectrum disorders in rodents: current status and future perspectives. Psychopharmacology. 2014;231(6):1125–46. PubMed DOI

Whitehouse CM, Lewis MH. Repetitive behavior in neurodevelopmental disorders: clinical and translational findings. Behav Anal. 2015;38(2):163–78. PubMed DOI PMC

Sundberg M, Sahin M. Cerebellar development and autism spectrum disorder in tuberous sclerosis complex. J Child Neurol. 2015;30(14):1954–62. PubMed DOI PMC

Niu M, Han Y, Dy ABC, Du J, Jin H, Qin J, et al. Autism symptoms in fragile X syndrome. J Child Neurol. 2017;32(10):903–9. PubMed DOI

Jamain S, Radyushkin K, Hammerschmidt K, Granon S, Boretius S, Varoqueaux F, et al. Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism. Proc Natl Acad Sci U S A. 2008;105(5):1710–5. PubMed DOI PMC

Betancur C, Buxbaum JD. SHANK3 haploinsufficiency: a common but underdiagnosed highly penetrant monogenic cause of autism spectrum disorders. Mol Autism. 2013;4:17. PubMed DOI PMC

Radyushkin K, Hammerschmidt K, Boretius S, Varoqueaux F, El-Kordi A, Ronnenberg A, et al. Neuroligin-3-deficient mice: model of a monogenic heritable form of autism with an olfactory deficit. Genes Brain Behav. 2009;8(4):416–25. PubMed DOI

Specchio N, Pietrafusa N, Trivisano M, Moavero R, De Palma L, Ferretti A, et al. Autism and epilepsy in patients with tuberous sclerosis complex. Front Neurol. 2020;11:639. PubMed DOI PMC

Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med. 2006;355(13):1345–56. 10.1056/NEJMra055323 PubMed

Kútna V, O’Leary VB, Newman E, Hoschl C, Ovsepian SV. Revisiting brain tuberous sclerosis complex in rat and human: shared molecular and cellular pathology leads to distinct neurophysiological and behavioral phenotypes. Neurotherapeutics. 2021;18(2):845–58. PubMed DOI PMC

Jeste SS, Varcin KJ, Hellemann GS, Gulsrud AC, Bhatt R, Kasari C, et al. Symptom profiles of autism spectrum disorder in tuberous sclerosis complex. Neurology. 2016;87(8):766–72. PubMed DOI PMC

Gadad BS, Hewitson L, Young KA, German DC. Neuropathology and animal models of autism: genetic and environmental factors. Autism Res Treat. 2013;2013:731935. PubMed PMC

Palavra F, Robalo C, Reis F. Recent advances and challenges of mTOR inhibitors use in the treatment of patients with tuberous sclerosis complex. Oxidative Med Cell Longev. 2017;2017(1):9820181. PubMed DOI PMC

Switon K, Kotulska K, Janusz-Kaminska A, Zmorzynska J, Jaworski J. Molecular neurobiology of mTOR. Neuroscience. 2017;341:112–53. PubMed DOI

Lipton JO, Sahin M. The neurology of mTOR. Neuron. 2014;84(2):275–91. PubMed DOI PMC

Eker R, Mossige J. A dominant gene for renal adenomas in the rat. Nature. 1961;189(4767):858–9. DOI

Yeung RS, Xiao GH, Jin F, Lee WC, Testa JR, Knudson AG. Predisposition to renal carcinoma in the Eker rat is determined by germ-line mutation of the tuberous sclerosis 2 (TSC2) gene. Proc Natl Acad Sci USA. 1994;91(24):11413–6. PubMed DOI PMC

Granak S, Tuckova K, Kutna V, Vojtechova I, Bajkova L, Petrasek T, et al. Developmental effects of constitutive mTORC1 hyperactivity and environmental enrichment on structural synaptic plasticity and behaviour in a rat model of autism spectrum disorder. Eur J Neurosci. 2023;57(1):17–31. PubMed DOI

Chi OZ, Wu CC, Liu X, Rah KH, Jacinto E, Weiss HR. Restoration of normal cerebral oxygen consumption with rapamycin treatment in a rat model of autism–tuberous sclerosis. Neuromolecular Med. 2015;17(3):305–13. PubMed DOI PMC

Chi OZ, Liu X, Fortus H, Werlen G, Jacinto E, Weiss HR. Inhibition of p70 ribosomal S6 kinase (S6K1) reduces cortical blood flow in a rat model of autism-tuberous sclerosis. Neuromolecular Med. 2024;26(1):10. PubMed DOI PMC

Kútna V, Uttl L, Waltereit R, Krištofiková Z, Kaping D, Petrásek T, et al. Tuberous sclerosis (tsc2+/-) model Eker rats reveals extensive neuronal loss with microglial invasion and vascular remodeling related to brain neoplasia. Neurotherapeutics. 2020;17(1):329–39. PubMed DOI PMC

Von Der Brelie C, Waltereit R, Zhang L, Beck H, Kirschstein T. Impaired synaptic plasticity in a rat model of tuberous sclerosis. Eur J Neurosci. 2006;23(3):686–92. PubMed DOI

Takahashi DK, Dinday MT, Barbaro NM, Baraban SC. Abnormal cortical cells and astrocytomas in the Eker rat model of tuberous sclerosis complex. Epilepsia. 2004;45(12):1525–30. PubMed DOI

Waltereit R, Japs B, Schneider M, de Vries PJ, Bartsch D. Epilepsy and Tsc2 haploinsufficiency lead to autistic-like social deficit behaviors in rats. Behav Genet. 2011;41(3):364–72. PubMed DOI

Schneider M, de Vries PJ, Schönig K, Rößner V, Waltereit R. mTOR inhibitor reverses autistic-like social deficit behaviours in adult rats with both Tsc2 haploinsufficiency and developmental status epilepticus. Eur Arch Psychiatry Clin Neurosci. 2017;267(5):455–63. PubMed DOI

Petrasek T, Vojtechova I, Klovrza O, Tuckova K, Vejmola C, Rak J, et al. mTOR inhibitor improves autistic-like behaviors related to Tsc2 haploinsufficiency but not following developmental status epilepticus. J Neurodev Disord. 2021;13:14. PubMed DOI PMC

Angoa-Pérez M, Kane MJ, Briggs DI, Francescutti DM, Kuhn DM. Marble burying and nestlet shredding as tests of repetitive, compulsive-like behaviors in mice. J Vis Exp. 2013;(82):50978. PubMed PMC

Kozlova AA, Rubets E, Vareltzoglou MR, Jarzebska N, Ragavan VN, Chen Y, et al. Knock-out of the critical nitric oxide synthase regulator DDAH1 in mice impacts amphetamine sensitivity and dopamine metabolism. J Neural Transm (Vienna). 2023;130(9):1097–112. PubMed DOI PMC

Thomas A, Burant A, Bui N, Graham D, Yuva-Paylor LA, Paylor R. Marble burying reflects a repetitive and perseverative behavior more than novelty-induced anxiety. Psychopharmacology. 2009;204(2):361–73. PubMed DOI PMC

Campeau S. Apparatus and general methods for exposing rats to audiogenic stress. Bio Protoc. 2016;6(21):e1994. PubMed DOI PMC

Valsamis B, Schmid S. Habituation and prepulse inhibition of acoustic startle in rodents. J Vis Exp. 2011;55:3446. PubMed PMC

Bouwknecht JA, Spiga F, Staub DR, Hale MW, Shekhar A, Lowry CA. Differential effects of exposure to low-light or high-light open-field on anxiety-related behaviors; relationship to c-Fos expression in serotonergic and non-serotonergic neurons in the dorsal raphe nucleus. Brain Res Bull. 2007;72(1):32–43. PubMed DOI PMC

Commons KG, Cholanians AB, Babb JA, Ehlinger DG. The rodent forced swim test measures stress-coping strategy, not depression-like behavior. ACS Chem Neurosci. 2017;8(5):955–60. PubMed DOI PMC

Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol. 1978;47(4):379–91. PubMed DOI

Slattery DA, Cryan JF. Using the rat forced swim test to assess antidepressant-like activity in rodents. Nat Protoc. 2012;7(6):1009–14. PubMed DOI

Guariglia SR, Chadman KK. Water T-maze: a useful assay for determination of repetitive behaviors in mice. J Neurosci Methods. 2013;220(1):24–9. PubMed DOI

Meyerolbersleben L, Winter C, Bernhardt N. Dissociation of wanting and liking in the sucrose preference test in dopamine transporter overexpressing rats. Behav Brain Res. 2020;378:112244. PubMed DOI

Hadar R, Edemann-Callesen H, Reinel C, Wieske F, Voget M, Popova E, et al. Rats overexpressing the dopamine transporter display behavioral and neurobiological abnormalities with relevance to repetitive disorders. Sci Rep. 2016;6(1):39145. PubMed DOI PMC

Winslow JT, Camacho F. Cholinergic modulation of a decrement in social investigation following repeated contacts between mice. Psychopharmacology. 1995;121(2):164–72. PubMed DOI

Kelly PH, Seviour PW, Iversen SD. Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res. 1975;94(3):507–22. PubMed DOI

Blanca MJ, Alarcón R, Arnau J, Bono R, Bendayan R. Non-normal data: is ANOVA still a valid option? Psicothema. 2017;29(4):552–7. PubMed DOI

Sun J, Yuan Y, Wu X, Liu A, Wang J, Yang S, et al. Excitatory SST neurons in the medial paralemniscal nucleus control repetitive self-grooming and encode reward. Neuron. 2022;110(20):3356–73.e8. PubMed DOI

Muehlmann AM, Lewis MH. Abnormal repetitive behaviours: shared phenomenology and pathophysiology. J Intellect Disabil Res. 2012;56(5):427–40. PubMed DOI

Moy SS, Riddick NV, Nikolova VD, Teng BL, Agster KL, Nonneman RJ, et al. Repetitive behavior profile and supersensitivity to amphetamine in the C58/J mouse model of autism. Behav Brain Res. 2014;259:200–14. PubMed PMC

Kim H, Lim CS, Kaang BK. Neuronal mechanisms and circuits underlying repetitive behaviors in mouse models of autism spectrum disorder. Behav Brain Funct. 2016;12(1):3. PubMed DOI PMC

Gandhi T, Lee CC. Neural mechanisms underlying repetitive behaviors in rodent models of autism spectrum disorders. Front Cell Neurosci. 2021;14:592710. PubMed DOI PMC

Parr-Brownlie LC, Hyland BI. Bradykinesia induced by dopamine D2 receptor blockade is associated with reduced motor cortex activity in the rat. J Neurosci. 2005;25(24):5700–9. PubMed DOI PMC

Kalueff AV, Stewart AM, Song C, Berridge KC, Graybiel AM, Fentress JC. Neurobiology of rodent self-grooming and its value for translational neuroscience. Nat Rev Neurosci. 2016;17(1):45–59. PubMed DOI PMC

de Brouwer G, Fick A, Harvey BH, Wolmarans DW. A critical inquiry into marble-burying as a preclinical screening paradigm of relevance for anxiety and obsessive-compulsive disorder: mapping the way forward. Cogn Affect Behav Neurosci. 2019;19(1):1–39. PubMed DOI

Taylor GT, Lerch S, Chourbaji S. Marble burying as compulsive behaviors in male and female mice. Acta Neurobiol Exp (Wars). 2017;77(3):254–60. PubMed DOI

Vaccarino F, Franklin KBJ. Self-stimulation and circling reveal functional differences between medial and lateral substantia nigra. Behav Brain Res. 1982;5(3):281–95. PubMed DOI

Abbott AE, Linke AC, Nair A, Jahedi A, Alba LA, Keown CL, et al. Repetitive behaviors in autism are linked to imbalance of corticostriatal connectivity: a functional connectivity MRI study. Soc Cogn Affect Neurosci. 2018;13(1):32–42. PubMed DOI PMC

Kim IH, Rossi MA, Aryal DK, Racz B, Kim N, Uezu A, et al. Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine. Nat Neurosci. 2015;18(6):883–91. PubMed DOI PMC

Goorden SMI, van Woerden GM, van der Weerd L, Cheadle JP, Elgersma Y. Cognitive deficits in Tsc1+/–mice in the absence of cerebral lesions and seizures. Ann Neurol. 2007;62(6):648–55. PubMed DOI

Reith RM, McKenna J, Wu H, Hashmi SS, Cho SH, Dash PK, et al. Loss of PubMed

Pearson B, Pobbe R, Defensor E, Oasay L, Bolivar V, Blanchard D, et al. Motor and cognitive stereotypies in the BTBR T + tf/J mouse model of autism. Genes Brain Behav. 2011;10(2):228–35. PubMed DOI PMC

Shin W, Kweon H, Kang R, Kim D, Kim K, Kang M, et al. Scn2a haploinsufficiency in mice suppresses hippocampal neuronal excitability, excitatory synaptic drive, and long-term potentiation, and spatial learning and memory. Front Mol Neurosci. 2019;12:145. PubMed DOI PMC

Bauer HF, Delling JP, Bockmann J, Boeckers TM, Schön M. Development of sex- and genotype-specific behavioral phenotypes in a Shank3 mouse model for neurodevelopmental disorders. Front Behav Neurosci. 2023;16:1051175. PubMed DOI PMC

Yoo T, Cho H, Lee J, Park H, Yoo YE, Yang E et al. GABA neuronal deletion of Shank3 exons 14–16 in mice suppresses striatal excitatory synaptic input and induces social and locomotor abnormalities. Front Cell Neurosci. 2018 Oct 9;12:341. PubMed PMC

Peça J, Feliciano C, Ting JT, Wang W, Wells MF, Venkatraman TN, et al. Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature. 2011;472(7344):437–42. PubMed DOI PMC

Jung S, Park M. Shank postsynaptic scaffolding proteins in autism spectrum disorder: mouse models and their dysfunctions in behaviors, synapses, and molecules. Pharmacol Res. 2022;182:106340. PubMed DOI

García-Villamisar D, Rojahn J. Comorbid psychopathology and stress mediate the relationship between autistic traits and repetitive behaviours in adults with autism. J Intellect Disabil Res. 2015;59(2):116–24. PubMed DOI

Katz RJ, Roth KA. Stress induced grooming in the rat–an endorphin mediated syndrome. Neurosci Lett. 1979;13(2):209–12. PubMed DOI

Homberg JR, Van Den Akker M, Raasø HS, Wardeh G, Binnekade R, Schoffelmeer ANM, et al. Enhanced motivation to self-administer cocaine is predicted by self-grooming behaviour and relates to dopamine release in the rat medial prefrontal cortex and amygdala. Eur J Neurosci. 2002;15(9):1542–50. PubMed DOI

Amodeo DA, Jones JH, Sweeney JA, Ragozzino ME. Differences in BTBR T + tf/J and C57BL/6J mice on probabilistic reversal learning and stereotyped behaviors. Behav Brain Res. 2012;227(1):64–72. PubMed DOI PMC

Whitehouse CM, Curry-Pochy LS, Shafer R, Rudy J, Lewis MH. Reversal learning in C58 mice: modeling higher order repetitive behavior. Behav Brain Res. 2017;332:372–8. PubMed DOI PMC

Solomon M, Smith AC, Frank MJ, Ly S, Carter CS. Probabilistic reinforcement learning in adults with autism spectrum disorders. Autism Res. 2011;4(2):109–20. PubMed DOI PMC

Min JY, Park S, Cho J, Huh Y. The anterior insular cortex processes social recognition memory. Sci Rep. 2023;13(1):10853. PubMed DOI PMC

Choleris E, Clipperton-Allen AE, Phan A, Valsecchi P, Kavaliers M. Estrogenic involvement in social learning, social recognition and pathogen avoidance. Front Neuroendocr. 2012;33(2):140–59. PubMed DOI

Kim SH, An K, Namkung H, Saito A, Rannals MD, Moore JR, et al. Anterior insula–associated social novelty recognition: pivotal roles of a local retinoic acid cascade and oxytocin signaling. AJP. 2023;180(4):305–17. PubMed DOI

Waltereit R, Welzl H, Dichgans J, Lipp HP, Schmidt WJ, Weller M. Enhanced episodic-like memory and kindling epilepsy in a rat model of tuberous sclerosis. J Neurochem. 2006;96(2):407–13. PubMed DOI

Werling DM, Geschwind DH. Sex differences in autism spectrum disorders. Curr Opin Neurol. 2013;26(2):146–53. PubMed DOI PMC

Leow KQ, Tonta MA, Lu J, Coleman HA, Parkington HC. Towards understanding sex differences in autism spectrum disorders. Brain Res. 2024;1833:148877. PubMed DOI

Jeon SJ, Gonzales EL, Mabunga DFN, Valencia ST, Kim DG, Kim Y, et al. Sex-specific behavioral features of rodent models of autism spectrum disorder. Exp Neurobiol. 2018;27(5):321–43. PubMed DOI PMC

Murta V, Seiffe A, Depino AM. Sex differences in mouse models of autism spectrum disorders: their potential to uncover the impact of brain sexual differentiation on gender Bias. Sexes. 2023;4(3):358–91. DOI

Bove M, Sikora V, Santoro M, Agosti LP, Palmieri MA, Dimonte S, et al. Sex differences in the BTBR idiopathic mouse model of autism spectrum disorders: behavioural and redox-related hippocampal alterations. Neuropharmacology. 2024;260:110134. PubMed DOI

El-Kordi A, Winkler D, Hammerschmidt K, Kästner A, Krueger D, Ronnenberg A, et al. Development of an autism severity score for mice using Nlgn4 null mutants as a construct-valid model of heritable monogenic autism. Behav Brain Res. 2013;251:41–9. PubMed DOI

Saré RM, Lemons A, Figueroa C, Song A, Levine M, Beebe Smith C. Sex-selective effects on behavior in a mouse model of tuberous sclerosis complex. eNeuro. 2020;7(2):ENEURO.0379-19.2020. PubMed PMC

Onda H, Lueck A, Marks PW, Warren HB, Kwiatkowski DJ. Tsc2+/– mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background. J Clin Invest. 1999;104(6):687–95. PubMed DOI PMC

Rennebeck G, Kleymenova EV, Anderson R, Yeung RS, Artzt K, Walker CL. Loss of function of the tuberous sclerosis 2 tumor suppressor gene results in embryonic lethality characterized by disrupted neuroepithelial growth and development. Proc Natl Acad Sci U S A. 1998;95(26):15629–34. PubMed DOI PMC

Zheng W, Wang M, Cui Y, Xu Q, Chen Y, Xian P, et al. Establishment of a two-hit mouse model of environmental factor induced autism spectrum disorder. Heliyon. 2024;10(9):e30617. PubMed DOI PMC

Li W, Pozzo-Miller L. Dysfunction of the corticostriatal pathway in autism spectrum disorders. J Neurosci Res. 2020;98(11):2130–47. PubMed DOI PMC

Morency MA, Stewart RJ, Beninger RJ. Effects of unilateral microinjections of sulpiride into the medial prefrontal cortex on circling behavior of rats. Prog Neuropsychopharmacol Biol Psychiatry. 1985;9(5):735–8. PubMed DOI

Kelly E, Meng F, Fujita H, Morgado F, Kazemi Y, Rice LC, et al. Regulation of autism-relevant behaviors by cerebellar–prefrontal cortical circuits. Nat Neurosci. 2020;23(9):1102–10. PubMed DOI PMC

Doll BB, Jacobs WJ, Sanfey AG, Frank MJ. Instructional control of reinforcement learning: a behavioral and neurocomputational investigation. Brain Res. 2009;1299:74–94. PubMed DOI PMC

Han S, Tai C, Jones CJ, Scheuer T, Catterall WA. Enhancement of inhibitory neurotransmission by GABAA receptors having α2,3-Subunits ameliorates behavioral deficits in a mouse model of autism. Neuron. 2014;81(6):1282–9. PubMed DOI PMC

O’Neill M, Brown VJ. The effect of striatal dopamine depletion and the adenosine A2A antagonist KW-6002 on reversal learning in rats. Neurobiol Learn Mem. 2007;88(1):75–81. PubMed DOI

Vanderschuren LJ, Schmidt ED, De Vries TJ, Van Moorsel CA, Tilders FJ, Schoffelmeer AN. A single exposure to amphetamine is sufficient to induce long-term behavioral, neuroendocrine, and neurochemical sensitization in rats. J Neurosci. 1999;19(21):9579–86. PubMed DOI PMC

Taracha E, Czarna M, Turzyńska D, Maciejak P. Amphetamine-induced prolonged disturbances in tissue levels of dopamine and serotonin in the rat brain. Pharmacol Rep. 2023;75(3):596–608. PubMed DOI PMC

Blum K, Bowirrat A, Sunder K, Thanos PK, Hanna C, Gold MS, et al. Dopamine dysregulation in reward and autism spectrum disorder. Brain Sci. 2024;14(7):733. PubMed DOI PMC

Sato M, Nakai N, Fujima S, Choe KY, Takumi T. Social circuits and their dysfunction in autism spectrum disorder. Mol Psychiatry. 2023;28(8):3194–206. PubMed DOI PMC