Selective changes of neurotransmitter receptors in middle-aged gerbil brain.

Age-related alterations in major neurotransmitter receptors and voltage dependent calcium channels were analyzed by receptor autoradiography in the gerbil brain. [3H]Quinuclidinyl benzilate (QNB), [3H]cyclohexyladenosine (CHA), [3H]muscimol, [3H]MK-801, [3H]SCH 23390, [3H]naloxone, and [3H]PN200-110 were used to label muscarinic acetylcholine receptors, adenosine A1 receptors, gamma-aminobutyric acidA (GABAA) receptors, N-methyl-D-aspartate (NMDA) receptors, dopamine D1 receptors, opioid receptors, and voltage dependent calcium channels, respectively. In middle-aged gerbils (16 months old), the hippocampus exhibited a significant elevation in [3H]QNB, [3H]MK-801, [3H]SCH 23390, [3H]naloxone, and [3H]PN200-110 binding, whereas [3H]CHA and [3H]muscimol binding showed a significant reduction in this area, compared with that of young animals (1 month). On the other hand, the cerebellum showed a significant alteration in [3H]QNB, [3H]CHA, and [3H]naloxone binding and the striatum also exhibited a significant alteration in [3H]SCH 23390 and [3H]CHA binding in middle-aged gerbils. The neocortex showed a significant elevation only in [3H]CHA binding in middle-aged animals. The nucleus accumbens and thalamus also showed a significant alteration only in [3H]muscimol binding. However, the hypothalamus and substantia nigra exhibited no significant alteration in these bindings in middle-aged gerbils. These results demonstrate the age-related alterations of various neurotransmitter receptors and voltage dependent calcium channels in most brain regions. Furthermore, they suggest that the hippocampus is most susceptible to aging processes and is altered at an early stage of senescence.