ROLES OF OPIOID PEPTIDES IN THE REGULATION OF HIPPOCAMPAL EXCITABILITY

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Roles of opioid peptides in the regulation of hippocampal excitability are a subject of intensive study since the discovery of endogenous opiates in the brain. Opiate peptides produce wet dog shakes (WDS) and epileptiform discharges in rats when administered intraventricularly. The purpose of this study was to obtain further information to support the hypothesis that opioid peptides in the hippocampus may play a role in mediating WDS and seizures activities. Injections of specific mu receptor agonist, (N-MePhe3, D-Pro)-morphiceptin (PL017), and delta receptor agonist, (D-Ala2, D-Leu5)-enkephalin (DADLE), to the ventral hippocampus produced convulsive seizures and numerous WDS, suggesting that both receptors are involved in the mediation of these behaviors. The levels of hippocampal glycine and gamma-aminobutyric acid (GABA) were increased but aspartate was reduced after PL017 injection. Pretreatment with beta-funaltrexamine hydrochloride (B-FNA), an irreversible mu receptor blocker, attenuated PL017-induced WDS and convulsions. It also restored the PL017-induced changes in the levels of hippocampal amino acids to that of control values. These results suggest that opiate-induced WDS and convulsive seizures are receptor mediated and may be acting through a disinhibition mechanism by attenuating the release of inhibitory amino acids in the hippocampus. Nevertheless, the degeneration of hippocampal granule cells by intrahippocampal injection of colchicine attenuated PL017-induced WDS but potentiated the severity of convulsions, therefore suggesting that these two behaviours may be mediated by different pathways in the hippocampus. These data give further evidence to the idea that opioid peptides in the hippocampus may play an important role in regulating hippocampal excitability. Studies are planned to determine the effects of opioid peptides on the turnover or in vivo release of GABA to directly test the hypothesis that GABA may mediate the excitability effect of opioid peptides in the hippocampus.