title: Object recognition impairment and rescue by a dopamine D2 antagonist in hyperdopaminergic mice.
abstract: 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 24h later. This deficit was compensated by a single 0.05mg/kg haloperidol injection 30min before training. In all mice, a 0.3mg/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.
authors.affiliation: Brain Institute, Federal University of Rio Grande do Norte, RN 59056-450, Brazil.
authors.forename: Arthur S C
authors.initials: AS
authors.lastname: França
authors.affiliation: Biochemistry Department, Federal University of Rio Grande do Norte, Brazil.
authors.forename: Larissa
authors.initials: L
authors.lastname: Muratori
authors.affiliation: Medical Engineering Department, Federal University of Rio Grande do Norte, Brazil.
authors.forename: George Carlos
authors.initials: GC
authors.lastname: Nascimento
authors.affiliation: Edmond & Lily Safra International Institute of Neuroscience of Natal, Brazil.
authors.forename: Catia Mendes
authors.initials: CM
authors.lastname: Pereira
authors.affiliation: Brain Institute, Federal University of Rio Grande do Norte, RN 59056-450, Brazil.
authors.forename: Sidarta
authors.initials: S
authors.lastname: Ribeiro
authors.affiliation: Biophysics and Pharmacology Department, Federal University of Rio Grande do Norte, RN 59078-970, Brazil. Electronic address: brunolobaosoares@gmail.com.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lobão-Soares
mesh_terms: D000818:Animals; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology* / Q000627:therapeutic use*; D008569:Memory Disorders / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D021641:Recognition, Psychology / Q000187:drug effects*; D018709:Statistics, Nonparametric
chemical_list: D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D006220:Haloperidol
keywords: DAT-KO; Dopamine; Haloperidol; Heterozygous; Object recognition