Regional age-related alterations in cholinergic and GABAergic receptors in the rat brain

The age-related changes of cholinergic and gamma-aminobutyric acid (GABA)ergic receptors were studied in 3-week- and 6-, 12-, 18- and 24-month-old Fisher 344 male rat brains using receptor autoradiography. [3H]Quinuclidinyl benzilate (QNB), [3H]hemicholinium-3 (HC) and [3H]muscimol were used to label acetylcholine receptors, acetylcholine reuptake sites and GABAA receptors, respectively. In immature rats (3-week-old), [3H]QNB and [3H]muscimol binding showed a significant increase in most brain areas, compared to adult young animals (6-month-old), whereas [3H]HC binding exhibited a significant increase only in the dentate gyrus, substantia nigra and cerebellum. In contrast, [3H]QNB and [3H]HC binding showed no significant changes in all brain areas during aging. On the other hands, [3H]muscimol binding showed a significant reduction in the substantia nigra and cerebellum of adult mature rats (12-month-old). Thereafter, the age-related reduction in [3H]muscimol binding was observed in all brain areas of aged rats (24-month-old). Our results demonstrate that the GABAergic system is susceptible to aging processes in the central nervous system, whereas the cholinergic system is unaltered by aging. Furthermore, our results suggest significant regional changes in both GABAergic and cholinergic systems in the brain even 3 weeks after birth. These findings suggest that the disturbance in GABAergic-cholinergic interactions may play a key role in age-related neurological deficits and cognitive dysfunction.