The development of epilepsy and a progressive increase in susceptibility to
seizures may involve changes in inhibitory and excitatory systems from the
beginning of the process. The present study was focused to analyze the opi
oid peptide changes induced by a chemical sub-convulsant stimulation. Exper
iments were carried out to determine opioid peptide release, mu receptor bi
nding and proenkephalin expression in rat brain, as well as nociceptive res
ponses, following the administration of a sub-convulsant dose of pentylenet
etrazol (PTZ) (30 mg/kg, i.p.). Membrane binding experiments revealed reduc
ed number of mu binding sites (B-max) in cortex and amygdala, but not in st
riatum and hippocampus, an effect that was evident only 24 h, but not 28 da
ys, after PTZ treatment. In situ hybridization experiments suggested a sign
ificant enhancement of proenkephalin mRNA expression in specific brain regi
ons 24 h after PTZ treatment. Microdialysis combined with a universal opioi
d peptide radioimmunoassay revealed extracellular opioid peptide levels to
be elevated in the amygdala (137%) 90 min after PTZ administration. Evaluat
ion of nociceptive responses using the Randall-Selitto test showed an analg
esic effect short term (30-90 min) after PTZ injection. Collectively, these
data provide evidence for a significant activation of opioid peptide syste
ms as a consequence of the administration of a sub-convulsant dose of PTZ.
These neurochemical changes may play an important role in the progression o
f epileptogenesis. (C) 1999 Elsevier Science B.V. All rights reserved.