2005; Freitas et al. 2005, 2008, 2009; Felippotti et al. 2011a). Thus, the outputs to the dH from the endogenous pain modulatory system nuclei shown in this study may reflect their involvement in postictal antinociception through the modulation of the activity of hippocampal outputs. The varicose monoaminergic, glutamatergic, and cholinergic axons are equipped with neuronal nicotinic

acetylcholine receptors and these nonsynaptically localized receptors are of high affinity. The activation of the receptor itself causes depolarization #Imatinib mw keyword# of the neuron, release of chemical transmitters, and may result in the modulation of neurotransmitter release initiated by axonal firing (Vizi and Lendvai 1999). The modulation of presynaptic nicotinic receptors in the neurochemical circuitry of the brain and brainstem areas that are interconnected with the dH, as presently shown, can provide a cholinergic mechanism that recruits other nuclei of the brainstem involved in monoaminergic descending control of pain Inhibitors,research,lifescience,medical and can activate complex neuronal assemblies that elaborate epileptogenic activity in the CNS, resulting in subsequent postictal antinociception (Coimbra et al. 2001a,b; Shouse et al. 2001; De

Freitas et al. 2004; Inhibitors,research,lifescience,medical Ferreira et al. 2005; Freitas et al. 2005, 2008, 2009; De Oliveira Inhibitors,research,lifescience,medical et al. 2006, 2011; Felippotti et al. 2011a,b, 2012). The present data corroborate findings from Klamt and Prado (1991), who showed that the microinjection of carbachol, a muscarinic cholinergic receptor agonist, into the Trichostatin A hippocampus causes

antinociception and decreases pain-related behavior in rats (Klamt and Inhibitors,research,lifescience,medical Prado 1991). In fact, in the current study, PTZ caused tonic–clonic seizures followed by antinociception, which was decreased by the inactivation of the dH and by the local blockade of cholinergic muscarinic and nicotinic receptors in the dH. These findings support the concept that the neurotransmitter acetylcholine may be involved in the antinociceptive process in seizures that are evoked by GABA-mediated Cl− influx blockade. Given that the administration of cholinergic Drug_discovery muscarinic and nicotinic receptors antagonists at the highest dose did not exert a significant influence on the baseline nociceptive threshold of the rodents, our data indicate that the intrahippocampal effects of these drugs were due to their specific action on postictal antinociception. A recent report showed that pretreatment with bicuculline partially prevents nicotine-induced antinociception, suggesting that the GABAA receptor may contribute to acetylcholine-mediated analgesia (Mui et al. 1997). Others have suggested that the GABAergic system may modulate nicotinic receptor-mediated seizures (Dobelis et al. 2003).