Abstracts

At present, the role of nociceptin/orphanin (N/OFQ) in seizure activity is controversial. The main goal of the present study was to analyze the effects of i.c.v administration of N/OFQ on partial and generalized seizures induced by amigdala kindling, as well as on the postictal depression after stage V kindled seizures, in rats. N/OFQ (0.003, 0.03, 0.3, 3, 30 nmolas, i.c.v.), alone or in combination with Nphe1-nociceptin(1-13)NH2 (30 nmolas, i.c.v.) (an antagonist of the ORL1) or naloxone (2 mg/kg, i.p.) was applied in adult male Wistar rats that previously received daily kindling electric stimulation and achieved partial (stage II, n=8) and generalized (kindled, n=8) seizures. Ten minutes after N/OFQ administration, the electrical current necessary to induce an afterdischarge (afterdischarge threshold, ADT) was determined. In addition, the susceptibility for subsequent seizures during the postictal depression in fully kindled rats was evaluated after presenting a kindled seizure, using a recycling paradigm. Control animals were manipulated as described above, except that they did not received electrical stimulation. In control animals, the administration of N/OFQ did not modify the ADT. In animals with partial seizures, the N/OFQ decreased in a dose dependent way the ADT (up to 45%), an effect that was blocked by Nphe1-nociceptin(1-13)NH2 and partially blocked by naloxone. In kindled animals, the administration of N/OFQ enhanced in a dose dependent way the ADT (up to 68%), effect that was blocked by Nphe1-nociceptin(1-13)NH2 and naloxone pretreatment. Concerning the evaluation of the postictal period in kindled animals, it was found that N/OFQ reduced the susceptibility for subsequent seizures (up to 48%), an effect that was blocked by Nphe1-nociceptin(1-13)NH2. The N/OFQ is able to modify the afterdischarge threshold in animals with partial and generalized seizures induced by amygdale kindling. The effects of this peptide depend on the type of seizures. In partial seizures, it increases the seizure susceptibility, an effect that could involve the activation different opioid receptors. In generalized seizures, N/OFQ reduces the seizure susceptibility and enhances the refractoriness for subsequent seizures during the postical depression. These later effects may be mediated by the N/OFQ receptor. (Supported by CONACyT fellowship 1148.)