EFFECT OF IDEBENONE ON IN-VIVO SEROTONIN RELEASE AND SEROTONERGIC RECEPTORS IN YOUNG AND AGED RATS

The effect of idebenone on the serotonergic system was evaluated in th e aging rat by measuring the kinetic constants of H-3-5HT and H-3-keta nserin binding sites in the cerebral cortex of rats at 3, 15 and 24 mo nths of age following acute and subchronic administration of the drug. Idebenone displayed no in vitro affinity toward any population of ser otonin receptors and did not modify their kinetic parameters after a s ingle dose of 100 mg/kg at any age tested. A subchronic treatment with the drug for 21 days at the dose of 30 mg/kg did not induce any relev ant change in 3- and 15-month-old rats, whereas it significantly incre ased the density of both H-3-5HT and H-3-ketanserin binding sites in 2 4-month-old rats, where a lower number of receptors is detected as a c onsequence of aging. This effect was rather specific, since under the same experimental conditions no changes were detected in the density o f cortical beta-adrenergic receptors in aged animals. In microdialysis studies, acute administration with idebenone did not affect 5HT and 5 HIAA release at any age. Conversely, the pattern of serotonin metaboli sm was significantly modified in aged rats following repeated treatmen t with idebenone and was partially restored to a value similar to the one observed in young animals. These results suggest that idebenone, a putative neuroprotective agent which has been shown to improve brain metabolism in ischemic conditions, might also attenuate age-associated neuronal damage, acting probably on several neurotransmitter systems which undergo selective modification during aging.