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, γ-aminobutyric acid_A (GABA_A) receptors, (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.