Peptides DBI 42-50 (DRPGLLDLK) and
DBI 43-50 (RPGLLDLK) are synthetic fragments of an 18
amino acid peptide called
octadecaneuropeptide (QATVGDVNTDRPGLLDLK), a brain derivative of
diazepam-binding inhibitor (
DBI). The two
peptides were unilaterally injected into the dorsal hippocampus (granule cells of dentate gyrus) of freely moving adult rats. The electroencephalographic (EEG) pattern was continuously recorded from bilateral hippocampal and cortical
electrodes, and the animals' behavior was observed throughout the experiment. A dose of 100 nmol
peptide 42-50 was required to reliably cause EEG alterations (
seizures and spiking). EEG changes, defined as
seizures, were characterized by discrete repetitive periods of high-frequency and/or multispike complexes and/or high-voltage synchronized spike or wave activity. EEG
seizures were often associated with a frozen appearance of the animal and "wet dog shakes."
Tonic-clonic convulsions were not observed. EEG
seizures induced by
peptide 42-50 were prevented by 90 mg/kg
PK 11195, a selective antagonist of a novel GABAA receptor-linked subtype of a
benzodiazepine (BDZ) receptor, but were unaffected by
flumazenil, an agonist of the "central" type of BDZ receptor and by D(-)2-amino-7-phosphonoheptanoic
acid, a selective antagonist of the
N-methyl-D-aspartate subtype of
excitatory amino acid receptors. Light microscopy showed no neuropathological changes in the injected hippocampus. The data show that these
DBI-derived
peptide fragments induce a typical pattern of limbic
seizures in rats.
DBI and/or its natural processing products may play a role in the pathophysiology of
epilepsy.