Ventral hippocampal dentate granule cell lesions enhance motor seizures but reduce wet dog shakes induced by mu opioid receptor agonist

Abstract

The role of the ventral hippocampal dentate granule neurons in the mu opioid receptor agonist-induced motor seizures and wet dog shakes was examined in this study. [NMe-Phe 3- d-Pro 4morphiceptin (9.4 nmol) was injected into the left ventral hippocampus of rats 14 days after unilateral or bilateral colchicine (5 nmol/site) lesions of ventral hippocampal dentate granule cells and the subsequent behavioral and neuropathological responses were observed. [NMe-Phe 3- d-Pro 4morphiceptin injected into control animals produced convulsions and numerous wet dog shakes that lasted for Jess than 1 h. [NMe-Phe 3- d-Pro 4morphiceptin-induced wet dog shakes were significantly reduced in unilateral colchicine-pretreated rats, and completely inhibited in bilateral colchicine-pretreated animals. In contrast, generalized motor seizures evoked by [NMe-Phe 3- d-Pro 4morphiceptin were potentiated and prolonged in colchicine-pretreated animals as status epilepticus (sustained clonus of forepaws and head for more than 1 h) was observed in both unilateral and bilateral colchicine-pretreated animals but not in control rats. No morphological damage of granule or pyramidal cells was found in the ventral hippocampus of control animals following [NMe-Phe 3- d-Pro 4morphiceptin injection. Colchicine treatment by itself produced a selective lesion of dentate granule cells. In colchicine-pretreated animals, [NMe-Phe 3- d-Pro 4morphiceptin induced widespread seizure-related damage of CA3/CA1 pyramidal cells. These results suggest that dentate granule cells in the ventral hippocampus are essential for the elaboration of wet dog shakes. However, these neurons may play an inhibitory role in the spread of seizure activity within the hippocampus or limbic structures. Neuronal damage produced by [NMe-Phe 3- d-Pro 4morphiceptin after colchicine treatment may be resulted from sustained seizure activity rather than direct neurotoxicity of the drug. Thus, the ventral hippocampus is an important site in eliciting both wet dog shakes and convulsions by a mu opioid receptor agonist, but the expression of these two behaviors does not depend on a common pathway.