Effect of Unilateral Perinatal Hypoxic‐Ischemic Brain Injury in the Rat on Striatal Muscarinic Cholinergic Receptors and High‐Affinity Choline Uptake Sites: A Quantitative Autoradiographic Study

The binding characteristics and distribution of M 1 and M 2 muscarinic cholinergic receptors and high‐affinity choline uptake sites were studied in the striatum of the rat at 3–4 and 9–12 weeks of age after exposure to unilateral perinatal hypoxic‐ischemic brain injury. High‐affinity choline uptake sites were labeled with [ 3 H]hemicholinium‐3, M 1 receptors with [ 3 H]pirenzepine, and M 2 receptors with [ 3 H]AFDX 116. Saturation experiments revealed a significant decrease in the maximal binding capacity ( B max ) for [ 3 H]pirenzepine‐labeled M 1 receptors in the lesioned caudate/putamen complex in immature rats with moderate brain injury, in comparison with controls. In contrast, the B max value for [ 3 H]hemicholinium‐3‐labeled high‐affinity choline uptake sites was significantly increased. No changes in dissociation constants ( K D ) were observed. These changes were most pronounced in the dorsolateral region of striatum. Striatal regional distribution of [ 3 H]AF‐DX 116 was not affected. In mature rats, binding of [ 3 H]pirenzepine returned to control values, whereas [ 3 H]hemicholinium binding showed a persistent increase (23%). The increase in [ 3 H]hemicholinium‐3 binding, as a specific marker of cholinergic nerve terminals, is consistent with our prior morphologic studies demonstrating relative preservation of cholinergic neurons and neuropil, and supports the concept that Striatal cholinergic systems are resistant to hypoxic‐ischemic injury.