Quantitative autoradiographic analysis of muscarinic cholinergic and adenosine A1 binding sites after transient forebrain ischemia in the gerbil

The influence of transient forebrain ischemia on adenosine A1 and muscarinic cholinergic receptors in the gerbil brain 1-27 days after recirculation was studied. The topographical distribution and the alteration in the adenosine A1 and muscarinic receptor sites were analyzed by means of quantitative receptor autoradiography using [3H]cyclohexyladenosine ([3H]CHA) and [3H]quinuclidinyl benzilate ([3H]QNB), respectively. In most regions examined, the temporal profiles of the alteration of the receptor density were in accordance with the histopathological findings. [3H]CHA binding activity decreased suddenly after neuronal damage, while [3H]QNB grain density showed a gradual decrease in the dorsolateral caudate-putamen and in the CA1 subfield of the hippocampus. In the caudate-putamen, [3H]CHA and [3H]QNB binding activity in the dorsal aspect was markedly reduced 1-27 days after ischemia. [3H]CHA binding activity in the ventromedial region of the caudate-putamen also decreased 1-3 days after ischemia, though neuronal damage was restricted to the dorsolateral aspect. Neuronal death in CA1 was preceded by the decrease in [3H]QNB binding activity in the stratum radiatum 1 and 2 days after ischemia. Marked decrease in [3H]QNB and [3H]CHA binding activity was noted in the CA1 subfield 3-27 days after recirculation. Three to 27 days after ischemia, the A1 binding activities in the CA3 subfield of the hippocampus and in the dentate gyrus were reduced despite the normal appearance of these areas throughout the reperfusion period. Muscarinic binding sites in the CA3 subfield were also reduced 27 days after ischemia. Despite minimal neuronal damage in the lateral septal nucleus and in the substantia nigra, the A1 binding activity in these regions was reduced by 70% and 50%, respectively. These results provide further evidence that the muscarinic receptors in the dorsolateral region of the caudate-putamen are localized postsynaptically on small and medium-sized neurons and that those in the CA1 subfield of the hippocampus are localized on the CA1 pyramidal cells.