Effect of idebenone on
in vivo serotonin release and serotonergic receptors in young and aged rats.
Scavini C, Rozza A, Lanza E,
Favalli L, Racagni G, Brunello N.
Institute of Pharmacology,
University of Pavia, Italy.
Eur Neuropsychopharmacol 1996 May;6(2):95-102
Abstract
The effect of idebenone on the
serotonergic system was evaluated in the aging rat by measuring the kinetic
constants of 3H-5HT and 3H-ketanserin binding sites in the cerebral cortex of
rats at 3, 15 and 24 months of age following acute and subchronic
administration of the drug. Idebenone displayed no in vitro affinity toward
any population of serotonin receptors and did not modify their kinetic
parameters after a single 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
relevant change in 3- and 15-month-old rats, whereas it significantly
increased the density of both 3H-5HT and 3H-ketanserin binding sites in
24-month-old rats, where a lower number of receptors is detected as a
consequence of aging. This effect was rather specific, since under the same
experimental conditions no changes were detected in the density of cortical
beta-adrenergic receptors in aged animals. In microdialysis studies, acute
administration with idebenone did not affect 5HT and 5HIAA release at any age.
Conversely, the pattern of serotonin metabolism was significantly modified in
aged rats following repeated treatment 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.
