ORIGINAL INVESTIGATION Role of β2-containing nicotinic acetylcholine receptors in auditory event-related potentials Noam D. Rudnick & Christine Koehler & Marina R. Picciotto & Steven J. Siegel Received: 30 July 2008 / Accepted: 26 September 2008 # Springer-Verlag 2008 Abstract Rationale Nicotine improves sensory processing in schizo- phrenic individuals, as measured by changes in auditory event-related potentials (ERPs). Nicotine administration also alters ERPs in mice by increasing the amplitude and gating of the P20 ERP component while decreasing the amplitude of the N40 ERP component. Less is known about the role of specific nicotinic acetylcholine receptor (nAChR) subtypes. Objectives In this study, we examined whether nAChRs containing the β2 subunit contribute to nicotine’ s effects on auditory ERPs. Materials and methods We tested the effect of nicotine in wild-type mice and mice lacking the β2 nAChR subunit. Mice underwent stereotaxic implantation of stainless steel electrodes located in the CA3 region of the hippocampus, and 50 paired click stimuli were delivered during each drug condition. Results There was no significant difference in P20 or N40 amplitude or gating between genotypes during the control condition, suggesting that β2-containing receptors are not essential for the baseline auditory ERP response. Nicotine increased P20 amplitude and enhanced gating in wild-type and β2 knockout mice, but only decreased N40 amplitude in wild-type mice. There was no effect of nicotine on N40 gating in either genotype. Conclusions β2-containing receptors are necessary for nicotine’ s effects on the N40 component of the mouse auditory ERP. These results suggest that β2-containing nAChRs modulate sensory processing and may serve as a therapeutic target in schizophrenic individuals. Keywords Nicotine . Nicotinic acetylcholine receptor . EEG . Event-related potentials . Auditory gating . Knockout mice . Hippocampus Introduction Individuals with psychiatric illness frequently exhibit abnor- malities in sensory processing that can be detected by measuring electroencephalographic (EEG) responses to auditory stimuli. These auditory event-related potentials (ERPs) contain positive and negative components called the P50 and N100, which show significant test–retest reliability (Rentzsch et al. 2008). When two auditory stimuli are presented in rapid succession, healthy subjects exhibit larger P50 and N100 responses to the first stimulus (S1) than the second (S2). This gating mechanism is disrupted in conditions such as schizophrenia and bipolar disorder (Brockhaus-Dumke et al. 2008; Sanchez-Morla et al. 2008). Nicotine reverses P50 gating deficits in schizophrenic individuals and their first-degree relatives and augments P50 gating in nonpsychiatric controls (Adler et al. 1992, 1993; Crawford et al. 2002). Amplitude of the N100 component is Psychopharmacology DOI 10.1007/s00213-008-1358-6 N. D. Rudnick : C. Koehler : S. J. Siegel (*) Stanley Center for Experimental Therapeutics, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19312, USA e-mail: siegels@upenn.edu M. R. Picciotto Department of Psychiatry, Yale University, New Haven, CT 06511, USA S. J. Siegel Transdisciplinary Tobacco Use Research Center, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19312, USA