1 The present study examined the eect of a range of doses of chronic nicotine (0.75, 1.5, 3.0 and 30.0 mg kg 71 day
71, s.c., 14 days) upon striatal dopaminergic nerve terminal survival following 6-hydroxydopamine (6-OHDA; 10 mg intrastriatal unilaterally) in rats; and the eects of acute nicotine (1 ) nicotine doses signi®cantly inhibited 6-OHDA-induced degeneration. 4 In wild-type mice, acute nicotine treatment produced signi®cant inhibition of methamphetamineinduced neurodegeneration. In a4 nAChR subunit knockout mice, acute nicotine treatment failed to inhibit methamphetamine-induced neurodegeneration. 5 Nicotine is capable of protecting dopaminergic neurons against Parkinsonian-like neurodegeneration in vivo. In rats, this neuroprotective eect is critically dependent upon nicotine dose and is consistent with the activation of nAChRs, as high, desensitizing doses of nicotine fail to be neuroprotective. Further, neuroprotection is absent in a4 nAChR subunit knockout mice. The current results therefore suggest that activation of a4 subunit containing nAChRs constitutes a major component of the neuroprotective eect of nicotine upon Parkinsonian-like damage in vivo.