Object recognition impairment and rescue by a dopamine D2 antagonist in hyperdopaminergic mice

Autor(es)

Franca, Arthur S. C. ^[1] ; Muratori, Larissa ^[2] ; Nascimento, George Carlos ^[3] ; Pereira, Catia Mendes ^[4] ; Ribeiro, Sidarta ^[1] ; Lobao-Soares, Bruno ^[5]

Afiliação do(s) autor(es)

^[1] Univ Fed Rio Grande do Norte, Inst Brain, BR-59056450 Natal, RN - Brazil

^[2] Univ Fed Rio Grande do Norte, Dept Biochem, Natal, RN - Brazil

^[3] Univ Fed Rio Grande do Norte, Med Engn Dept, Natal, RN - Brazil

^[4] Edmond & Lily Safra Int Inst Neurosci Natal, Natal, RN - Brazil

^[5] Univ Fed Rio Grande do Norte, Biophys & Pharmacol Dept, BR-59078970 Natal, RN - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Behavioural Brain Research; v. 308, p. 211-216, JUL 15 2016.
• Citações Web of Science: 5

Resumo

Genetically-modified mice without the dopamine transporter (DAT) are hyperdopaminergic, and serve as models for studies of addiction, mania and hyperactive disorders. Here we investigated the capacity for object recognition in mildly hyperdopaminergic mice heterozygous for DAT (DAT +/-), with synaptic dopaminergic levels situated between those shown by DAT -/- homozygous and wild-type (WT) mice. We used a classical dopamine D2 antagonist, haloperidol, to modulate the levels of dopaminergic transmission in a dose-dependent manner, before or after exploring novel objects. In comparison with WT mice, DAT +/- mice showed a deficit in object recognition upon subsequent testing 24 h later. This deficit was compensated by a single 0.05 mg/kg haloperidol injection 30 min before training. In all mice, a 0.3 mg/kg haloperidol injected immediately after training impaired object recognition. The results indicate that a mild enhancement of dopaminergic levels can be detrimental to object recognition, and that this deficit can be rescued by a low dose of a D2 dopamine receptor antagonist. This suggests that novel object recognition is optimal at intermediate levels of D2 receptor activity. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 13/07699-0 - Centro de Pesquisa, Inovação e Difusão em Neuromatemática - NeuroMat
• Beneficiário: Oswaldo Baffa Filho
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs