Inhibition of the dopamine transporter as an animal model of bipolar disorder mania: Locomotor response, neuroimmunological profile and pharmacological modulation

Publication date: Available online 6 April 2018 Source:Journal of Psychiatric Research Author(s): Juliana R. Bastos, Katherinne M. Perico, Érica L. Marciano Vieira, Antônio L. Teixeira, Fabiana S. Machado, Aline S. de Miranda, Fabrício A. Moreira Inhibition of dopamine transporter (DAT) by GBR12909 has been proposed as a pharmacological model of mania related to bipolar disorder (BD). Here we tested the hypothesis that GBR12909 injection impairs habituation and induces hyperlocomotion in mice, along with changes in cytokines and neurotrophic factors levels, as observed in BD patients. We also tested if lithium carbonate, sodium valproate and aripiprazole prevent GBR12909-induced locomotion. Male Swiss mice received GBR12909 (15 mg/kg) injections and locomotor responses were quantified in an open field. Cytokines and neurotrophic factors levels were assessed in the prefrontal cortex, striatum and hippocampus 30 min and 24 h after injections. Pre-treatments with lithium, valproate or aripiprazole were performed with single and repeated injection protocols. GBR12909 prevented motoric habituation and increased basal locomotion in habituated mice in the open field. This compound also induced changes in IL-2 and BDNF levels in prefrontal cortex; IL-2, IL-4 and IL-10 in striatum; and IL-10, IL-4, IFN-γ and NGF in hippocampus. GBR12909-induced hyperlocomotion was attenuated by lithium (12.5–100 mg/kg), but not valproate (75–300 mg/kg), and prevented by arip...
Source: Journal of Psychiatric Research - Category: Psychiatry Source Type: research