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Pregabalin- and topiramate-mediated regulation of cognitive and motor impulsivity in DBA/2 mice

AuthorsNavarrete, Francisco; Pérez-Ortiz, José Manuel; Manzanares, Jorge
Issue Date2012
PublisherNature Publishing Group
CitationBritish Journal of Pharmacology 167(1): 183-195 (2012)
AbstractBACKGROUND AND PURPOSE Impulsivity is a core symptom in many neuropsychiatric disorders. The main objective of this study was to evaluate the effects of topiramate and pregabalin on the modulation of different impulsivity dimensions in DBA/2 mice. EXPERIMENTAL APPROACH The effects of acute and chronic administration of pregabalin (10, 20 and 40 mg·kg -1) and topiramate (12.5, 25 and 50 mg·kg -1) were evaluated in the light-dark box (LDB), hole board test (HBT) and delayed reinforcement task (DRT). α 2A-Adrenoceptor, D 2-receptor and TH gene expression were evaluated by real-time PCR in the prefrontal cortex (PFC), accumbens (ACC) and ventral tegmental area (VTA), respectively. KEY RESULTS Acute pregabalin administration showed a clear anxiolytic-like effect (LDB) but did not modify novelty-seeking behaviour (HBT). In contrast, topiramate produced an anxiolytic effect only at the highest dose, whereas it reduced novelty seeking at all doses tested. In the DRT, acute pregabalin had no effect, whereas topiramate only reduced motor impulsivity. Chronically, pregabalin significantly increased motor impulsivity and topiramate diminished cognitive impulsivity. Pregabalin decreased α 2A-adrenoceptor and D 2-receptor gene expression in the PFC and ACC, respectively, and increased TH in the VTA. In contrast, chronic administration of topiramate increased α 2A-adrenoceptor and D 2-receptor gene expression in the PFC and ACC, respectively, and also increased TH in the VTA. CONCLUSIONS AND IMPLICATIONS These results suggest that the usefulness of pregabalin in impulsivity-related disorders is related to its anxiolytic properties, whereas topiramate modulates impulsivity. These differences could be linked to their opposite effects on α 2A-adrenoceptor and D 2-receptor gene expression in the PFC and ACC, respectively. © 2012 The British Pharmacological Society.
ISSNissn: 0007-1188
E-ISSNe-issn: 1476-5381
Identifiersdoi: 10.1111/j.1476-5381.2012.01981.x
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