The modulation of striatal dopamine release correlates with water-maze performance in aged rats.

Abstract Cluster analysis of performance during acquisition of a place-learning task in the water maze distinguished between subpopulations of aged rats (25–27 months) classified as moderately (AMI) or severely impaired (ASI) in comparison with young adults (3–5 months). Using a slice-superfusion device, electrically or nicotine-evoked release of dopamine from striatum was assessed in the presence of GR-55,562 (5-HT 1B receptor antagonist), methiotepin (mixed 5-HT 1/2 receptor antagonist) and/or sulpiride ( D 2 / D 3 receptor antagonist). The main neuropharmacological results demonstrated age-related alterations in the 5-HT 1B - and D 2 / D 3 -mediated modulation of electrically evoked striatal dopamine release. Regression analyses indicated a possible contribution of such alterations to the age-related behavioural deficits: the larger the deficit, the weaker the electrically evoked release under 5-HT 1B and D 2 / D 3 receptor blockade. Extending our recent report on the modulation of striatal acetylcholine release in aged rats [Cassel et al., 2007. Neurobiol. Aging 28, 1270–1285], these new findings make dopaminergic and serotonergic functional alterations potential candidates to participate in age-related deficits in the water maze, most probably in interaction with formerly described cholinergic dysfunctions.