Pmg. NeurwPsychophommcol. & Eiol. Psychiot. 1988. Vol. 12. pp. 337-344 027S-584S&l$0.00 + so Printed in Great Britain. All rIghta reserved Copyright @ 1988 Pergamon Press plc zyxwvu AGE-RELATED CHANGES IN GABA AND BENZODIAZEPINE RECEPTOR BINDING IN RAT BRAIN ARE INFLUENCED BY SAMPLING TIME LENNARD P. NILES, OLGA M. PULIDO and DARRYL S. PICKERING Department of Neurosciences, McMaster University Hamilton, Ontario, Canada (Final form, July, 1987) Abstract Lennard P. Niles, Olga M. Pulido and Darryl S. Pickering: Age-related changes in GABA and benzodiazepine receptor binding in rat brain are influenced by sampling time. Prog . Neuro-Psychopharmacol. & Biol. Psychiat. 1988, 12:337-344 - 1. 2. 3. 4. 5. This study examined the saturation binding of tritiatedraminobutyric acid zyxwvutsrqponmlkjihgfedcb ([3H]GA13A) and [allldiazepam in brain membranes from young (3 month-old) and aged (21-23 month- old) Long Evans male rats killed at two time points in the 24-hour cycle. The daytime density of low-affinity GABA binding sites was significantly (pt0.051 lower in cortical membranes from aged animals. There were no differences between young and old rats in low-affinity GABA binding at night, or in high-affinity GABA binding at either time point. Diazepam binding was significantly lower in the brains of aged animals killed during the daytime. There were no differences at night, when diazepam binding in Young animals declined to match that of aged animals. There were no differences in the affinities of either GABA or diazepam binding sites. These findings indicate that sampling time significantly influences age-associated changes in the densities of low-affinity GABA and diazepam binding sites. Therefore, the effects of age on brain receptor binding parameters should be measured at several points in the 24-hour light/dark cycle in order to control for possible age-related changes in binding rhythmicity. Key Words: Aging, Benzodiazepine binding sites, Brain, GABA binding sites, Sampling time Introduction Various studies have indicated changes in the characteristics of neurotransmitter receptors in the brains of aged mammals. A significant decrease in B-adrenergic receptor density has been observed in the cerebellum and brain stem of aged rats and in human cerebellum (Hagpi et al., 19791. Selective changes in receptors for various neurotransmitters such as dopamine, norepinephrine and y-aminobutyric acid (GABA), have also been reported (De Blasi et al., 19821. In a preliminary study we observed a 244 decrease in high affinity binding of the tritiated GABA agonist, [sH]muscimol, in the cerebral cortex of aged Long Evans rats (Niles and Pulido, 1986). Similar decreases in [aH]muscimol and [aH]GABA binding in male Wistar and Sprague-Dawley rat brains have been reported by other investigators who 337