The effect of cholinergic receptor blockade by scopolamine on memory performance and the auditory P3

previous research has suggested a possible link between the effects of scopolamine-induced muscarinic cholinergic receptor blockade on memory and its effect on auditory P3 amplitude and latency. A potential problem with this hypothesis is that, although scopolamine has been reported to increase P3 latency in both visual and auditory modalities, amplitude reductions have been reported only in the case of auditory P3 at Ct. In the present study, subjects were injected intravenously with 5.7 mu g/kg of scopolamine of saline in a double blind design. A significant reduction in verbal recognition memory performance was observed. This memory impairment was shown to be largely specific to the encoding of verbal material. The drug effect was of equal magnitude when words of either high or low word frequency were used. Auditory P3 was recorded from frontal central and parietal sites along the midline and over left and right hemispheres. In contrast to a number of earlier reports using a similar drug dose, only limited evidence was found of either latency increase or amplitude reduction of the auditory P3. Importantly, two potentially confounding drug-related ERP modulations were observed prior to and during the latency range of the P3. The first was a widespread increase in N2 amplitude and latency preceding the P3. The second was that ERPs became relatively more negative at frontal and central sites in the 200-450 ms latency range in both target and non-target conditions. Whether this effect is the result of an increase in negativity or a reduction in P3a amplitude remains to be determined. Interestingly, ERPs to target stimuli became significantly less positive at frontal sites in the drug condition in the latency range 400-900 ms. This is consistent with recent reports highlighting the importance of frontal regions in normal memory function. Previously hypothesized links between cholinergic receptor blockade, effects on P3 latency and amplitude, and drug-induced memory impairments are discussed in the light of these findings.