Administration of kainic acid and colchicine alters μ and λ opiate binding in rat hippocampus

Abstract

Quantitative in vitro autoradiography was used to assess the effects of kainic acid (KA) and colchicine (COL) on μ and λ opiate binding in the rat hippocampus. Rats were treated with either systemic KA, a neurotoxin that damages CA 3 pyramidal cells and causes seizures and wet-dog shakes, or intrahippocampal COL to destroy dentate granule cells and their mossy fibers, or both toxins. Moderate levels of μ binding were detected in the pyramidal layer and in the stratum lacunosum-moleculare; binding was greater in the ventral hippocampus. Levels of μ binding were markedly increased in all regions 48 h after treatment with KA. Two weeks after COL treatment, there was a modest decrease in μ binding; COL plus KA gave results similar to COL alone. Dense λ binding was present over the mossy fibers in the stratum lucidum, but was absent over the pyramidal layer. In contrast to μ binding, λ binding was greater in the dorsal hippocampus. KA alone had little effect on λ binding, whereas COL alone caused large decreases. KA plus COL caused even larger decreases in λ binding, to as much as 85% below control. These results demonstrate that μ and γ binding are localized to different parts of the hippocampus, respond differently to neurotoxin lesions, and likely serve different roles in this brain region. The number of μ sites is responsive to the release of enkephalin; these receptors appear to be linked to opiate-induced hippocampal seizure activity, especially wet-dog shakes. λ sites may serve as autoreceptors on mossy fibers.