Opioid peptide systems following a subconvulsant dose of pentylenetetrazol in rats

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 opioid peptide changes induced by a chemical sub-convulsant stimulation. Experiments were carried out to determine opioid peptide release, mu receptor binding and proenkephalin expression in rat brain, as well as nociceptive responses, following the administration of a sub-convulsant dose of pentylenetetrazol (PTZ) (30 mg/kg, i.p.). Membrane binding experiments revealed reduced number of mu binding sites (Bmax) in cortex and amygdala, but not in striatum and hippocampus, an effect that was evident only 24 h, but not 28 days, after PTZ treatment. In situ hybridization experiments suggested a significant enhancement of proenkephalin mRNA expression in specific brain regions 24 h after PTZ treatment. Microdialysis combined with a universal opioid peptide radioimmunoassay revealed extracellular opioid peptide levels to be elevated in the amygdala (137%) 90 min after PTZ administration. Evaluation of nociceptive responses using the Randall-Selitto test showed an analgesic effect short term (30-90 min) after PTZ injection. Collectively, these data provide evidence for a significant activation of opioid peptide systems as a consequence of the administration of a sub-convulsant dose of PTZ. These neurochemical changes may play an important role in the progression of epileptogenesis.