{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:12Z","timestamp":1787028552513,"version":"build-2736575974"},"reference-count":76,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Neurological Foundation of New Zealand","award":["1625-PG"],"award-info":[{"award-number":["1625-PG"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. However, the core biology of the disorder that leads to the hypofunctioning of the cerebral dopaminergic network requires further elucidation. We investigated midbrain synaptic changes in male rats exposed to repeated hypoxia during the equivalent of extreme prematurity, which is a new animal model of the hyperactive\/impulsive presentation of ADHD. We used a novel combination of a lentiviral vector, peroxidase-immunonanogold double-labelling, three-dimensional serial section transmission electron microscopy and stereological techniques to investigate the synapses formed between GABAergic axons of the rostromedial tegmental nucleus (RMTg) and dopaminergic neurons of the posterior ventral tegmental area (pVTA). This is a key site that sends extensive dopaminergic projections to the forebrain. We also compared the results to our previous study on a schizophrenia risk factor that produces cerebral hyperdopaminergia. In total, 117 reconstructed synapses were compared. Repeated hypoxic rats had a significantly thicker (22%) and longer (18%) postsynaptic density at RMTg GABAergic-pVTA dopaminergic synapses compared to their controls. These results were opposite to those previously observed in rats exposed to a schizophrenia risk factor. These findings for repeated hypoxic rats suggest that the enhanced inhibition of pVTA dopaminergic neurons may contribute to hypodopaminergia in ADHD motor hyperactivity. Synaptic triads, a key component of pVTA circuitry, were not detected in repeated hypoxic rats, indicating a marked deficit. The current knowledge may guide development in males of novel, site-specific ADHD drugs, which is necessary due to the rising prevalence of ADHD, the chronic nature of ADHD symptoms and the limitations of the currently available medications.<\/jats:p>","DOI":"10.3390\/ijms252312970","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T13:34:04Z","timestamp":1733146444000},"page":"12970","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Risk Factor for Attention Deficit Hyperactivity Disorder Induces Marked Long-Term Anatomical Changes at GABAergic-Dopaminergic Synapses in the Rat Ventral Tegmental Area"],"prefix":"10.3390","volume":"25","author":[{"given":"Steve","family":"Seo","sequence":"first","affiliation":[{"name":"Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand"},{"name":"Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise C.","family":"Parr-Brownlie","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand"},{"name":"Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand"},{"name":"Brain Research, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hollie E.","family":"Wicky","sequence":"additional","affiliation":[{"name":"Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand"},{"name":"Brain Research, Dunedin 9054, New Zealand"},{"name":"Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1256-4888","authenticated-orcid":false,"given":"David K.","family":"Bilkey","sequence":"additional","affiliation":[{"name":"Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand"},{"name":"Department of Psychology, University of Otago, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7142-0040","authenticated-orcid":false,"given":"Stephanie M.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand"},{"name":"Brain Research, Dunedin 9054, New Zealand"},{"name":"Department of Biochemistry, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0212-4456","authenticated-orcid":false,"given":"Dorothy E.","family":"Oorschot","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand"},{"name":"Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1001\/archpsyc.62.6.593","article-title":"Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication","volume":"62","author":"Kessler","year":"2005","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/S0140-6736(19)33004-1","article-title":"Attention-deficit hyperactivity disorder","volume":"395","author":"Posner","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (APA) (2013). Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Publishing. [5th ed.].","DOI":"10.1176\/appi.books.9780890425596"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Luo, Y., Weibman, D., Halperin, J.M., and Li, X. (2019). A review of heterogeneity in attention deficit\/hyperactivity disorder (ADHD). Front. Hum. Neurosci., 13.","DOI":"10.3389\/fnhum.2019.00042"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ivanov, I., Bjork, J.M., Blair, J., and Newcorn, J.H. (2022). Sensitization-based risk for substance abuse in vulnerable individuals with ADHD: Review and re-examination of evidence. Neurosci. Biobehav. Rev., 135.","DOI":"10.1016\/j.neubiorev.2022.104575"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1177\/1060028013510699","article-title":"A review of the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD)","volume":"48","author":"Sharma","year":"2014","journal-title":"Ann. Pharmacother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11065-007-9019-9","article-title":"Etiologic subtypes of attention deficit\/hyperactivity disorder: Brain imaging, molecular genetic and environmental factors and the dopamine hypothesis","volume":"17","author":"Swanson","year":"2007","journal-title":"Neuropsychol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"36","DOI":"10.21037\/tp.2017.08.02","article-title":"Pharmacologic management of attention deficit hyperactivity disorder in children and adolescents: A review for practitioners","volume":"7","author":"Brown","year":"2017","journal-title":"Transl. Pediatr."},{"key":"ref_9","first-page":"13","article-title":"Real-world data on attention deficit hyperactivity disorder medication side effects","volume":"7","author":"Cascade","year":"2010","journal-title":"Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1080\/14740338.2017.1389894","article-title":"Pediatric pharmacoepidemiology-safety and effectiveness of medicines for ADHD","volume":"16","author":"Clavenna","year":"2017","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_11","first-page":"1543","article-title":"Adherence, persistence, and medication discontinuation in patients with attention-deficit\/hyperactivity disorder-a systematic literature review","volume":"10","author":"Gajria","year":"2014","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1007\/s00787-018-1125-0","article-title":"Efficacy and safety of drugs for attention deficit hyperactivity disorder in children and adolescents: A network meta-analysis","volume":"27","author":"Padilha","year":"2018","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1089\/cap.2005.15.799","article-title":"Attention-deficit\/hyperactivity disorder, medication treatment, and substance use patterns among adolescents and young adults","volume":"15","author":"Upadhyaya","year":"2005","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.2165\/00023210-200923000-00004","article-title":"Efficacy and safety limitations of attention-deficit hyperactivity disorder pharmacotherapy in children and adults","volume":"23","author":"Wigal","year":"2009","journal-title":"CNS Drugs"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/nrn1406","article-title":"Dopamine, learning and motivation","volume":"5","author":"Wise","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.neuroscience.2008.02.003","article-title":"Organization of ventral tegmental area projections to the ventral tegmental area-nigral complex in the rat","volume":"153","author":"Ferreira","year":"2008","journal-title":"Neuroscience"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/nrn.2016.165","article-title":"Ventral tegmental area: Cellular heterogeneity, connectivity and behaviour","volume":"18","author":"Morales","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14094","DOI":"10.1523\/JNEUROSCI.3370-12.2012","article-title":"Braking dopamine systems: A new GABA master structure for mesolimbic and nigrostriatal functions","volume":"32","author":"Barrot","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"108763","DOI":"10.1016\/j.neuropharm.2021.108763","article-title":"The rostromedial tegmental (RMTg) \u201cbrake\u201d on dopamine and behavior: A decade of progress but also much unfinished work","volume":"198","author":"Zhou","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"560","DOI":"10.3109\/08039488.2014.892151","article-title":"Psychosis in adulthood is associated with high rates of ADHD and CD problems during childhood","volume":"68","author":"Dalteg","year":"2014","journal-title":"Nord. J. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1017\/S0033291714003183","article-title":"Persistence and remission of ADHD during adulthood: A 7-year clinical follow-up study","volume":"45","author":"Karam","year":"2015","journal-title":"Psychol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4529","DOI":"10.1523\/JNEUROSCI.16-14-04529.1996","article-title":"Synaptogenesis and Fos expression in the motor cortex of the adult rat after motor skill learning","volume":"16","author":"Kleim","year":"1996","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nature09552","article-title":"Rethinking schizophrenia","volume":"468","author":"Insel","year":"2010","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kohe, S.E., Gowing, E.K., Seo, S., and Oorschot, D.E. (2023). A novel rat model of ADHD-like hyperactivity\/impulsivity after delayed reward has selective loss of dopaminergic neurons in the right ventral tegmental area. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411252"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jneumeth.2007.01.010","article-title":"ADHD-like hyperactivity, with no attention deficit, in adult rats after repeated hypoxia during the equivalent of extreme prematurity","volume":"166","author":"Oorschot","year":"2007","journal-title":"J. Neurosci. Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11863","DOI":"10.1523\/JNEUROSCI.0342-12.2013","article-title":"Spectrum of short- and long-term brain pathology and long-term behavioral deficits in male repeated hypoxic rats closely resembling human extreme prematurity","volume":"33","author":"Oorschot","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1007\/s13311-012-0135-8","article-title":"The prevalence of DSM-IV attention-deficit\/hyperactivity disorder: A meta-analytic review","volume":"9","author":"Willcut","year":"2012","journal-title":"Neurotherapeutics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1001\/jama.288.6.728","article-title":"Cognitive and behavioral outcomes of school-aged children who were born preterm: A meta-analysis","volume":"288","author":"Bhutta","year":"2002","journal-title":"J. Am. Med. Assoc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9319","DOI":"10.1111\/j.1469-7610.1997.tb01612.x","article-title":"Attention deficit hyperactivity disorders and other psychiatric outcomes in very low birthweight children at 12 years","volume":"38","author":"Botting","year":"1997","journal-title":"J. Child Psychol. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1111\/j.1469-8749.1990.tb08117.x","article-title":"Psychiatric disorders at five years among children with birthweights less than 1000 g: A regional perspective","volume":"32","author":"Szatmari","year":"1990","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3946","DOI":"10.1002\/cne.25225","article-title":"A schizophrenia risk factor induces marked anatomical deficits at GABAergic-dopaminergic synapses in the rat ventral tegmental area: Essential evidence for new targeted therapies","volume":"529","author":"Seo","year":"2021","journal-title":"J. Comp. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1093\/schbul\/sbp006","article-title":"The dopamine hypothesis of schizophrenia: Version III-the final common pathway","volume":"35","author":"Howes","year":"2009","journal-title":"Schizophr. Bull."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/1477-7525-8-53","article-title":"Health related quality of life after extremely preterm birth: A matched controlled cohort study","volume":"8","author":"Vederhus","year":"2010","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1111\/ejn.16197","article-title":"Ultrastructural analysis of nigrostriatal dopaminergic terminals in a knockin mouse model of DYT1 dystonia","volume":"59","author":"Pan","year":"2024","journal-title":"Eur. J. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"E2410","DOI":"10.1073\/pnas.1716189115","article-title":"Long-term potentiation expands information content of hippocampal dentate gyrus synapses","volume":"115","author":"Bromer","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1002\/cne.23891","article-title":"Marked differences in the number and type of synapses innervating the somata and primary dendrites of midbrain dopaminergic neurons, striatal cholinergic interneurons and striatal spiny projection neurons in the rat","volume":"524","author":"Sizemore","year":"2016","journal-title":"J. Comp. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4834","DOI":"10.1523\/JNEUROSCI.4745-10.2011","article-title":"Trafficking of AMPA receptors at plasma membranes of hippocampal neurons","volume":"31","author":"Crocker","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Harris, K.M., and Weinberg, R.J. (2012). Ultrastructure of synapses in the mammalian brain. Cold Spring Harb. Perspect. Biol., 4.","DOI":"10.1101\/cshperspect.a005587"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.neuroscience.2010.03.050","article-title":"Glutamatergic axons from the lateral habenula mainly terminate on GABAergic neurons of the ventral midbrain","volume":"168","author":"Brinschwitz","year":"2010","journal-title":"Neuroscience"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/0006-8993(91)90312-J","article-title":"Perforated and non-perforated synapses in rat neocortex: Three-dimensional reconstructions","volume":"556","author":"Jones","year":"1991","journal-title":"Brain Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0301-0082(94)90040-X","article-title":"Are you using neuronal densities, synaptic densities or neurochemical densities are your definitive data? There is a better way to go","volume":"44","author":"Oorschot","year":"1994","journal-title":"Prog. Neurobiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Flores, C.E., and M\u00e9ndez, P. (2014). Shaping inhibition: Activity dependent structural plasticity of GABAergic synapses. Front. Cell. Neurosci., 8.","DOI":"10.3389\/fncel.2014.00327"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/25999","article-title":"Increased number of synaptic GABA(A) receptors underlies potentiation at hippocampal inhibitory synapses","volume":"395","author":"Nusser","year":"1998","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1800143","DOI":"10.1002\/adtp.201800143","article-title":"PDZ Domains Drug targets","volume":"2","author":"Christensen","year":"2019","journal-title":"Adv. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.tips.2018.04.003","article-title":"An emerging circuit pharmacology of GABAA receptors","volume":"39","author":"Engin","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1471-4159.2004.02271.x","article-title":"Identification of GABAA receptor subunit variants in midbrain dopaminergic neurons","volume":"89","author":"Okada","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S0896-6273(00)80382-7","article-title":"Differences in synaptic GABAA receptor number underlie variation in GABA mini amplitude","volume":"19","author":"Nusser","year":"1997","journal-title":"Neuron"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/cne.10741","article-title":"Synaptic organization of tooth pulp afferent terminals in the rat trigeminal sensory nuclei","volume":"463","author":"Bae","year":"2003","journal-title":"J. Comp. Neurol."},{"key":"ref_49","first-page":"259","article-title":"Serial and triadic synapses in the cerebellar nuclei of the cat","volume":"30","author":"Hamori","year":"1977","journal-title":"Exp. Brain Res."},{"key":"ref_50","first-page":"357","article-title":"An electron microscopic study of the centre-median and ventrolateral nuclei of the thalamus in the monkey","volume":"279","author":"Harding","year":"1977","journal-title":"Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.schres.2015.03.031","article-title":"Clinical and functional implications of a history of childhood ADHD in first-episode psychosis","volume":"165","author":"Rho","year":"2015","journal-title":"Schizophr. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.bbr.2014.11.032","article-title":"Acoustic noise improves motor learning in spontaneously hypertensive rats, a rat model of attention deficit hyperactivity disorder","volume":"280","author":"Holmblad","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0149-7634(99)00058-5","article-title":"Behavioral validation of the spontaneously hypertensive rat (SHR) as an animal model of attention-deficit\/hyperactivity disorder (AD\/HD)","volume":"24","author":"Sagvolden","year":"2000","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Katzav, A., Grigoriadis, N.C., Ebert, T., Touloumi, O., Blank, M., Pick, C.G., Shoenfeld, Y., and Chapman, J. (2013). Coagulopathy triggered autoimmunity: Experimental antiphospholipid syndrome in factor V Leiden mice. BMC Med. J., 11.","DOI":"10.1186\/1741-7015-11-92"},{"key":"ref_55","first-page":"101132","article-title":"Extreme prematurity: Risk and resiliency","volume":"52","author":"Taylor","year":"2022","journal-title":"Curr. Probl. Pediatr. Adolesc. Health Care"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e100823","DOI":"10.1136\/gpsych-2022-100823","article-title":"A glimpse of gender differences in schizophrenia","volume":"35","author":"Li","year":"2022","journal-title":"Gen. Psychiatry"},{"key":"ref_57","first-page":"127","article-title":"The neonatal testosterone surge: A comparative study","volume":"100","author":"Corbier","year":"1992","journal-title":"Arch. Int. Physiol. Biochim. Biophys."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/0091-3057(93)90555-8","article-title":"Sex differences in amphetamine-induced locomotor activity in adult rats: Role of testosterone exposure in the neonatal period","volume":"46","author":"Forgie","year":"1993","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0892-0362(94)90118-X","article-title":"Decreased postnatal testosterone and corticosterone concentrations in rats following acute intermittent prenatal hypoxia without alterations in adult male sex behavior","volume":"16","author":"Hermans","year":"1994","journal-title":"Neurotoxicology Teratol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1159\/000142387","article-title":"Global birth hypoxia increases the neonatal testosterone surge in the rat","volume":"88","author":"Boksa","year":"2008","journal-title":"Neuroendocrinology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/S0014-4886(03)00079-7","article-title":"Differential vulnerability of male versus female rats to long-term effects of birth insult on brain catecholamine levels","volume":"182","author":"Boksa","year":"2003","journal-title":"Exp. Neurol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.yfrne.2006.07.001","article-title":"Estrogen and the development and protection of nigrostriatal dopaminergic neurons: Concerted action of a multitude of signals, protective molecules, and growth factors","volume":"27","author":"Kipp","year":"2006","journal-title":"Front. Neuroendocrinol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.neubiorev.2014.03.014","article-title":"A systematic review and meta-analysis of the effects of antipsychotic medications on regional cerebral blood flow (rCBF) in schizophrenia: Association with response to treatment","volume":"43","author":"Handley","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_64","first-page":"56","article-title":"Exercise as a treatment for schizophrenia: A review","volume":"49","author":"Girdler","year":"2019","journal-title":"Psychopharmacol. Bull."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1152\/japplphysiol.00880.2004","article-title":"Tyrosine hydroxylase expression and activity in the rat brain: Differential regulation after long-term intermittent or sustained hypoxia","volume":"99","author":"Gozal","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1089\/hum.2011.026","article-title":"Lentiviral-mediated gene transfer to the sheep brain: Implications for gene therapy in Batten disease","volume":"22","author":"Linterman","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"ref_67","unstructured":"Paxinos, G., and Watson, C. (1998). The Rat Brain in Stereotaxic Coordinates, Academic Press. [4th ed.]."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/j.1750-3639.2008.00146.x","article-title":"Neonatal rat hypoxia-ischemia: Long-term rescue of striatal neurons and motor skills by combined antioxidant-hypothermia treatment","volume":"18","author":"Hobbs","year":"2008","journal-title":"Brain Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S0361-9230(01)00557-3","article-title":"Differential effects of unilateral striatal and nigrostriatal lesions on grip strength, skilled paw reaching and drug-induced rotation in the rat","volume":"55","author":"Jeyasingham","year":"2001","journal-title":"Brain Res. Bull."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0166-4328(97)00170-8","article-title":"Altered reinforcement mechanisms in attention-deficit\/hyperactivity disorder","volume":"94","author":"Sagvolden","year":"1998","journal-title":"Behav. Brain Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.baga.2013.04.001","article-title":"Synaptic connectivity between rat striatal spiny projection neurons in vivo: Unexpected multiple somatic innervation in the context of overall sparse proximal connectivity","volume":"3","author":"Oorschot","year":"2013","journal-title":"Basal Ganglia"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/j.1469-7580.2010.01264.x","article-title":"Number and type of synapses on the distal dendrite of a rat striatal cholinergic interneuron: A quantitative, ultrastructural study","volume":"217","author":"Sizemore","year":"2010","journal-title":"J. Anat."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/0301-0082(91)90007-N","article-title":"Neurite growth from, and neuronal survival within, cultured explants of the nervous system: A critical review of morphometric and stereological methods, and suggestions for the future","volume":"37","author":"Oorschot","year":"1991","journal-title":"Prog. Neurobiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1365-2818.1988.tb04610.x","article-title":"Comparison of methods for the estimation of the thickness of ultrathin tissue sections","volume":"151","year":"1988","journal-title":"J. Microsc."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1046\/j.1365-2818.2001.00926.x","article-title":"Cylindrical diameters method for calibrating section thickness in serial electron microscopy","volume":"202","author":"Fiala","year":"2001","journal-title":"J. Microsc."},{"key":"ref_76","unstructured":"Small, J.V. (1968, January 1\u20137). Meaurement of section thickness. Proceedings of the Abstracts of the Fourth European Regional Conference on Electron Microscopy, Rome, Italy."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/23\/12970\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:45:21Z","timestamp":1760114721000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/23\/12970"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,2]]},"references-count":76,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252312970"],"URL":"https:\/\/doi.org\/10.3390\/ijms252312970","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,2]]}}}