Abstracts

RATIONALE: At present it is unclear the mechanisms by which Gabapentin produces antiepileptic effects. However, evidence indicates that this drug enhances GABAergic neurotransmission and opioid peptide release. The present study was designed to determine if acute or subchronic administration of Gabapentin modifies benzodiazepine (BDZ) and opioid (m) receptor binding in the mouse brain. METHODS: Male CD1 mice received acute (100 mg/kg, v.o., n=5) or subchronic administration of Gabapentin (100 mg/kg, v.o. daily per 8 days, n=5). Control group received saline solution administration (0.1 ml/10 g, v.o., n=5). Animals were sacrified by decapitation 24 h after the last administration. Coronal brain frozen sections (20 mm) were obtained, and thereafter used for in vitro autoradiography experiments carried out to label BDZ ( 3H flunitrazepam, 2 nm) and m ( 3H DAMGO, 2 nM) receptor binding. RESULTS: Concerning BDZ receptors, acute administration of Gabapentin decreased receptor binding in the basolateral amygdala (30%), while subchronic treatment reduced receptor binding in frontal (20%) and parietal (35%) cortices; CA1-3 of Ammon s horn (34%) and basolateral amygdala (33%). About opioid receptors, the subchronic administration of Gabapentin decreased m receptor binding only in cingulate cortex (49%). CONCLUSIONS: The decreased BDZ receptor binding detected in the present study supports that Gabapentin modulates the GABAergic system.. On the other hand, an interaction between GABAergic and opioid peptide systems may explain the reduced m receptor binding following subchronic administration of this drug. (Partially supported by CONACyT 31702-M).