Regulation of dihydropyridine calcium antagonist binding sites in the rat hippocampus following neurochemical lesions

The effects of catecholaminergic, cholinergic, serotonergic, and glutaminergic terminal destruction and neurotransmitter depletion on [³H]nitrendipine binding to rat brain membranes were determined using the neurotoxins 6‐hydroxydopamine, 5,7‐dihydroxytryptamine, and kainic acid and the neurotransmitter‐depleting agent reserpine. Following intracisternal injection of 6‐hydroxydopamine there were time‐dependent increases (14–23%) in the density but not change in the affinity of hippocampal [³H]nitrendipine binding sites. 6‐Hydroxydopamine significantly increased [³H]nitrendipine binding in the hippocampus 4 and 10 days following injection. However, no significant change in binding was observed at 16 and 26 days. [³H]Nitrendipine binding in the cerebral cortex, striatum, cerebellum, and brain stem was unaffected by 6‐hydroxydopamine. Neither 5,7‐dihydroxytryptamine nor kainic acid affected [³H]nitrendipine binding in the hippocampus and cerebral cortex. Acute and chronic reserpinization also did not affect [³H]nitrendipine binding in the hippocampus and cerebral cortex. These results indicate that dihydropyridine calcium antagonist bindings sites in rat brain are subject to brain region‐specific regulation following neurochemical lesions and may be present in their largest densities on postsynaptic membranes.