Administration of kainic acid and colchicine alters mu and lambda opiate binding in rat hippocampus.
Quantitative in vitro autoradiography was used to assess the effects of kainic acid (KA) and colchicine (COL) on mu and lambda opiate binding in the rat hippocampus. Rats were treated with either systemic KA, a neurotoxin that damages CA3 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 mu binding were detected in the pyramidal layer and in the stratum lacunosum-moleculare; binding was greater in the ventral hippocampus. Levels of mu binding were markedly increased in all regions 48 h after treatment with KA. Two weeks after COL treatment, there was a modest decrease in mu binding; COL plus KA gave results similar to COL alone. Dense lambda binding was present over the mossy fibers in the stratum lucidum, but was absent over the pyramidal layer. In contrast to mu binding, lambda binding was greater in the dorsal hippocampus. KA alone had little effect on lambda binding, whereas COL alone caused large decreases. KA plus COL caused even larger decreases in lambda binding, to as much as 85% below control. These results demonstrate that mu and lambda 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 mu sites is responsive to the release of enkephalin; these receptors appear to be linked to opiate-induced hippocampal seizure activity, especially wet-dog shakes. Lambda sites may serve as autoreceptors on mossy fibers.
Perry
D C
DC
Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037.
Grimes
L M
LM
D000818:Animals; D001345:Autoradiography; D001425:Bacterial Outer Membrane Proteins; D003078:Colchicine / Q000494:pharmacology*; D004090:Dihydromorphine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000378:metabolism; D018272:Porins; D051381:Rats; D011916:Rats, Inbred F344; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017450:Receptors, Opioid, mu; D011991:Receptors, Virus / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D014316:Tritium
D001425:Bacterial Outer Membrane Proteins; D018272:Porins; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D011991:Receptors, Virus; C016532:maltoporins; D014316:Tritium; D009270:Naloxone; D004090:Dihydromorphine; D007608:Kainic Acid; D003078:Colchicine