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However, motor changes that are induced by unilateral 6\u2010OHDA injections may interfere with the identification of cognitive and affective dysfunctions induced by dopaminergic neurodegeneration. To select an appropriate method for studying nonmotor symptoms of PD and potential neuroprotective treatments, the present study compared behavioral effects of bilateral 6\u2010OHDA infusions directly in the substantia nigra pars compacta (SNpc) or striatum in rats. A battery of behavioral tests, including affective and cognitive tasks, was performed for 22\u2009days after 6\u2010OHDA nigrostriatal lesions. The massive degeneration of tyrosine hydroxylase\u2010immunoreactive neurons was observed in the SNpc, striatum, and ventral tegmental area with 6\u2010OHDA infusions in either the SNpc or striatum. Concerning functional outcomes, 6\u2010OHDA infusions in the striatum decreased general exploratory activity 7\u2009days after the lesion. Rats that received 6\u2010OHDA in the SNpc exhibited cognitive impairments and despair\u2010like behavior. A decrease in the number of newborn neurons was found in the hippocampus in rats that received 6\u2010OHDA in the striatum, indicating a alteration of neuron maturation. 6\u2010OHDA infusions in both the SNpc and striatum impacted the maturation of newborn hippocampal neurons. These results indicate that bilateral injections of 6\u2010OHDA in the SNpc might be useful for studying nonmotor symptoms of PD.<\/jats:p>","DOI":"10.1002\/jnr.70154","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:23:17Z","timestamp":1788841397000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Cognitive and Affective Outcomes Following Bilateral 6\u2010Hydroxydopamine Lesions of the Substance Nigra or Striatum in Rats"],"prefix":"10.1002","volume":"104","author":[{"given":"Bianca Andretto","family":"de Mattos","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics State University of Maring\u00e1  Maring\u00e1 Paran\u00e1 Brazil"},{"name":"Department of Physiology School of Medicine of Ribeir\u00e3o Preto  Ribeir\u00e3o Preto S\u00e3o Paulo 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