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Comparative effects of the dopaminergic agonists piribedil and bromocriptine in three different memory paradigms in rodents

Centre de Neurosciences Intégratives et Cognitives, CNRS UMR 5228, Université de Bordeaux 1, Talence, France, a.marighetto{at}lnc.u-bordeaux1.fr

S. Valerio

Centre de Neurosciences Intégratives et Cognitives, CNRS UMR 5228, Université de Bordeaux 1, Talence, France

JN Philippin

Centre de Neurosciences Intégratives et Cognitives, CNRS UMR 5228, Université de Bordeaux 1, Talence, France

V. Bertaina-Anglade

Preclinical Pharmacology Department, Biotrial, Rennes, France

C. Drieu la Rochelle

Preclinical Pharmacology Department, Biotrial, Rennes, France

R. Jaffard

Centre de Neurosciences Intégratives et Cognitives, CNRS UMR 5228, Université de Bordeaux 1, Talence, France

P. Morain

Institut de Recherches Internationales SERVIER, Courbevoie, France

The potential memory-enhancing properties of two dopamine agonists currently used in patients with Parkinson's disease, piribedil (1, 10 mg/kg/day, subcutaneously) and bromocriptine (5 mg/kg/day, subcutaneously), were evaluated in three experiments. Although piribedil (10 mg/kg) and bromocriptine equally enhanced spontaneous object recognition in young adult rats (experiment A), only piribedil displayed beneficial effects against aging-related memory impairments in two radial-maze experiments in mice. First (experiment B), a two-stage paradigm of spatial discrimination was used to assess relational/declarative memory in aged mice; piribedil (1 and 10 mg/kg) selectively and significantly improved the performances of aged mice in the critical tests for relational/declarative memory, whereas bromocriptine had no effect. Second, in a novel working memory task (experiment C), vehicle- or bromocriptine-treated aged mice displayed, compared with (vehicle) younger controls, a severe and persistent deficit in short-term retention of successive arm-visits, performing close to chance whichever the retention interval. Performances of piribedil (10 mg/kg) group remarkably improved across testing-days and reached young adults' level. The restoration of specific mnemonic impairments, in aged mice, highlights the memory-enhancing properties of piribedil. The efficacy of this drug in treating cognitive impairment of Parkinson's disease should now be assessed in more specific models.This work was published in an abstract form: ECNP Abstracts, 2005 (P8060 & P8065).

Key Words: spontaneous object recognition • relational/declarative memory • working memory • rat • mouse • aging

This version was published on July 1, 2008

Journal of Psychopharmacology, Vol. 22, No. 5, 511-521 (2008)
DOI: 10.1177/0269881107083836


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