P50 auditory evoked potentials from a control and schizophrenia patient. The arrows indicate the onset of the stimuli. The tick marks delineate the peak and trough of the P50 evoked response wave. In the normal subject, the test amplitude is 12% of the conditioning amplitude demonstrating the suppression of response to the second of paired identical tones. The schizophrenic patient shows a test amplitude of 84% of the responses of the conditioning amplitude. (Adapted from Adler et al 1990.)

A: The P50 auditory gating deficit in the relative of a schizophrenic patient (left upper panel) with a lack of inhibition. The arrows indicate the onset of the stimuli. The tick marks delineate the peak and trough of the P50 evoked response wave. The test amplitude is initially 161% of the conditioning amplitude. After nicotine gum, the P50 evoked response is normalized as indicated by a test amplitude of 37% of the conditioning amplitude (left lower panel); B: With pretreatment with mecamylamine (right upper panel) blockade of the α2ß4 high affinity receptor does not block the effect of nicotine(right lower panel) thus the test amplitude is 3% of the conditioning amplitude. The enhancement of the effect may be caused by mecamylamine’s blockade of the stimulatory effect of nicotine on catecholamine release, which is mediated through high affinity nicotinic receptors(Adapted from Freedman et al. 1994).

Auditory evoked potentials in response to identical paired stimuli in 2 inbred strains of mouse. The arrows indicate the onset of the stimuli. The tick marks delineate the peak and trough of the N40 evoked response wave. The C3H strain models the pattern seen with human control subjects with a test amplitude that is 17% of the conditioning amplitude, demonstrating inhibition of the evoked potential. The DBA/2 mouse shows a pattern similar to that observed in schizophrenia patients, with a test amplitude of 114% of the conditioning amplitude, and a lack of inhibition of the evoked response. . (From Stevens et al 1996).

A. The effect of DMXBA on the ratio of the amplitude of the second auditory evoked response divided by the amplitude of the response to the first stimulus. DMXBA dose dependently lowered the ratio showing improvement in auditory gating in the DBA/2 mouse, a model of schizophrenia-like deficits in auditory gating. DMXBA was administered as indicated by the arrows labeled injection. Asterisks indicate ratios that are significantly different from vehicle. Filled circles indicate mean N40 ratio B. DMXBA was administered as indicated by the arrows labeled injection.The improvement in auditory gating with this compound was produced by a selective decrease in the response to the second stimulus demonstrating increased inhibition in the circuitry. The records were obtained in the CA3 region of the hippocampus in response to paired identical auditory stimuli. The DMXBA was administered subcutaneous and recordings obtained at 5 minute intervals. At 40 minutes, when the responses were back to baseline levels, a second identical injection was administered and recordings were obtained for an additional 40 mintues. Filled circles indicate mean conditioning amplitude. Open circles indicate mean test amplitude. Asterisks indicate amplitudes that are significantly different from vehicle (Adapted from Stevens et al 1998).

Auditory evoked responses of a subject with schizophrenia. Stimuli were a conditioning auditory stimulus and an identical test stimulus, delivered 500 msec apart. Inhibition of the test P50 response is increased by DMXB-A administration, particularly during the lower dose (third row), compared to baseline and placebo responses above it. Arrows show the timing of the stimuli and vertical bars mark the location of the P50 wave in the tracings above. Positive polarity is downwards; vertical grid interval is 2 μV, and horizontal is 50 ms. (Adapted from Olincy et al. 2006).

Effects of DMXB-A and placebo on the RBANS Total Scale Score and its specific Indices. I is immediate and D is delayed Memory Visu-Spat=visuospatial memory. (Adapted from Olincy et al. 2006).