title: Baseline and 8-OH-DPAT-induced release of acetylcholine in the hippocampus of aged rats with different levels of cognitive dysfunction.
abstract: During aging, neurotransmission systems such as the cholinergic and serotonergic ones are altered. Using rats aged 3 or 24-26 months, this study investigated whether the well-described 8-OH-DPAT-induced increase of hippocampal acetylcholine release was altered in aged rats and whether it may vary according to the magnitude of age-related cognitive deficits. Long-Evans female rats aged 24-26 months were classified as good or bad performers on the basis of their reference-memory performance in a Morris water-maze task. Subsequently, the efficiency of 5-HT(1A) receptor agonist 8-OH-DPAT (0.5 mg/kg, s.c.) in triggering hippocampal acetylcholine release was evaluated by in vivo microdialysis and high performance liquid chromatography analysis. Besides a reduced baseline release in aged rats and a correlation between the baseline release and probe-trial performance in all rats, the results demonstrated that 8-OH-DPAT produced a significant increase of hippocampal acetylcholine release (peak value) in all rats, whether aged or young. While significant in bad performers (+56%), this increase did not reach significance in good performers (+32%). The results suggest that (i) some aspects of cognitive alterations related to aging might be linked to the baseline release of acetylcholine in the hippocampus, and (ii) the cholinergic innervation of the hippocampus of aged rats responds almost normally to systemic activation of 5-HT(1A) receptors, and (iii) differential alterations of cholinergic/serotonergic interactions assessed by determination of the 8-OH-DPAT-induced release of acetylcholine in the hippocampus could not be linked with clarity to the cognitive status of aged rats.
authors.affiliation: Laboratoire de Neurosciences Comportementales et Cognitives, U.M.R. 7521 Université Louis Pasteur/Centre National de la Recherche Scientifique, I.F.R. 37 de Neurosciences, 12 rue Goethe, 67000 Strasbourg, France.
authors.forename: Anelise
authors.initials: A
authors.lastname: Lazaris
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bertrand
authors.forename: Christine
authors.initials: C
authors.lastname: Lazarus
authors.forename: Rodrigue
authors.initials: R
authors.lastname: Galani
authors.forename: Jeanne
authors.initials: J
authors.lastname: Stemmelin
authors.forename: Raphaël
authors.initials: R
authors.lastname: Poirier
authors.forename: Christian
authors.initials: C
authors.lastname: Kelche
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Cassel
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000109:Acetylcholine / Q000378:metabolism*; D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D003072:Cognition Disorders / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011985:Receptors, Serotonin / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1
chemical_list: D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000109:Acetylcholine