Pentylenetetrazol-induced kindling: early involvement of excitatory and inhibitory systems

• Published in: Epilepsy research 1996-12, Vol.26 (1), p.105-113
• Main Authors: Rocha, L., Briones, M., Ackermann, R.F., Anton, B., Maidment, N.T., Evans, C.J., Engel, J.
• Format: Article
• Language: English
• Subjects: Amygdala - drug effects; Amygdala - metabolism; Animals; Behavior, Animal - drug effects; Benzodiazepine receptors; Chemical kindling; Dose-Response Relationship, Drug; Excitatory amino acids; Excitatory Amino Acids - metabolism; Hippocampus - drug effects; Hippocampus - metabolism; Kindling, Neurologic; Male; Mice; Motor Activity - drug effects; Opioid receptors; Pentylenetetrazol; Pentylenetetrazole - pharmacology; Rats; Rats, Wistar; Receptors, GABA-A - drug effects; Receptors, Opioid, delta - drug effects; Receptors, Opioid, mu - drug effects
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/S0920-1211(96)00046-0

Alterations in the brain of rats receiving a single non-convulsive administration pentylenetetrazol (PTZ), 30 mg/kg, i.p. (single PTZ group) were investigated and compared with those detected in fully PTZ kindled rats (chronic PTZ group). In vitro receptor autoradiography experiments showed that both single and chronic PTZ groups presented reduced mu opioid and benzodiazepine (BDZ) receptor binding in specific brain areas. Using an antibody generated against the delta opioid receptor (DOR-1), it was found that DOR-1 like immunoreactivity was reduced in cortex and amygdala of mice following single and chronic PTZ administration. Microdialysis experiments revealed that the administration of PTZ 30 mg/kg, i.p. in freely moving rats without previous experience with the drug, induces a rise in glutamate release, detected in the first and second 10 min dialysates collected from amygdala (138% and 50%, respectively) and frontal cortex (70% and 45%, respectively) as well as aspartate in frontal cortex in the first and second post-PTZ dialysates (143% and 80%, respectively). Subsequently, values returned to basal conditions. It may be speculated that decreased BDZ receptor binding results from enhanced release of GABA. On the other hand, the decrease of mu receptor binding and DOR-1 immunoreactivity observed after PTZ administration may be the result of enhanced levels of opioid peptides probably released over the kindling procedure. In conclusion, the present study indicates that PTZ-kindling is associated with an imbalance between excitatory and inhibitory systems which is apparent early in the epileptogenic process.