Nicotine (NIC) is neuroprotective against glutamate and hypoxia-induced neurotoxicity, preventing neuronal death and apoptosis in primary neuronal cultures. This effect is mediated by activation of both alpha7 and alpha4beta2 subtypes of nicotinic receptors for acetylcholine (nAChR) (Kaneko et al., 1997; Hejmadi et al., 2003). Furthermore, it seems that activation of alpha7 nAChR is the mechanism by which galantamine protects against thapsigargin and beta-amyloid-induced cell death (Arias et al., 2004), as well as in neuroprotection exerted by NIC against tumor necrosis factor alpha (Gahring et al., 2003). In this context we studied possible protection produced by NIC in an oxygen-glucose deprivation (OGD) model of rat and mouse hippocampal slices. The involvement of alpha7 nAChR in neuroprotection was proved by using wild-type and alpha7 knockout (KO) mice.