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P50 responses in normal subjects with sensory overloading
THURSDAY,, MAY 19
baseline startle amplitude, and since ALX does not reduce strychninepotentiated startle. The effects of alphaxalone on CRF-potentiated startle may not be generalized to all CRF-sfimulated behaviors, since alphaxalone failed to disrupt CRF-stimulated locomotor activity. CRF-potentiated startle is a useful assay for studying the effects of novel anxiolyfic agents, and alphaxalone appears to be a steroid anesthetic with anxiolytic properties in this assay.
59. SIMILAR EFFECTS OF STIMULANTS ON LATENT INHIBITION AND PREPULSE INHIBITION V.P. Bakshi, M.A. Geyer, N. Taaid, & N.R. Swerdlow Depts of Neuroscience and Psychiatry, UCSD School of Medicine, La Jolla, CA 92093-0804 Sensorimotor gating deficits characterize several neumpsychiatric disorders, including schizophrenia. Latent inhibition (LI) and prepulse inhibition (PPi) are used to study the neural subslxates underlying sensorimotor gating deficits, in LI, exposure to a stimulus retards the subsequent association of that stimulus with an event. In PPI, a subthreshold stimulus presented immediately prior to a startling stimulus inhibits or attenuates the startle response. Dopamine agnnists such as amphetamine disrupt both L! and PPi. Amphetamine has been reported to increase startle amplitude as well as exploratory locomotion. Such "non-specific" behavioral activation might complicate the interpretation of amphetamine-induced changes in PP! or LI. We compared the effects of three behaviorally activating drugs on LI and PPI. Separate groups of rats were treated with either vehicle, the dopamine releaser amphetamine (I .5 mg/kg, ip), the glycine antagnnist strychnine (0.75 mg/kg, ip), or the phosphodiesterase inhibitor caffeine (!0 mg/kg, sc), and then tested in either an active avoidance chamber (for LI) or startle chambers (for PPI). Locomotion was measured by inter-trial crossing in the avoidance chamber. As reported previously, amphetamine stimulated locomotion and disrupted both LI and PPi, but in this case did not elevate startle amplitude, in contrast, caffeine enhanced locomotion, but had no effect on LI or PPI. Strychnine produced only mild behavioral activation, significantly elevated startle amplitude, and significantly disrupted LI and PPI. These results suggest that neither increased startle amplitude nor locomotor activation are necessary or sufficient conditions for disruption of sensorimotor gating as measured by LI or PPI.
60. P50 RESPONSES IN NORMAL SUBJECTS WITH SENSORY OVERLOADING Y. Jin, S.G. Potkin, J. Wu, L. Tjahjono, & C. Sandman Department of Psychiatry, University of California Irvine Medical Center, Orange, CA 9266~ Schizophrenic patients have been reported to have a decreased sensory gating measured by high $2/SI ratio on the paired evoked potential (EP) responses. This study was proposed to develop a psychophysiological model of schizophrenia by sensory overloading. Conditioning-testing auditory PS0 EP was applied to 25 normal subjects (16 males and 9 females, age: 22.4 + 9.3). PS0 data for each subject was collected under two experimental conditions: a resting condition and a sensory overload condition. The sensory overload was produced by a series of random photic interferences. Consistent with the observation in schizophrenic patients, the ex-
B[OL PSYCHIATRY 631 1994,35:615-747
cessive sensory stimulation significantly attenuated the first conditioning !)50 response (p<0.001), while the second testing response was not changed (p-0.32). Consequently the C-T ratio was also significantly increased with the visual interference (p<0.05). These findings suggested that the amplitude of PS0, especially that to the first stimulus was dependent on the psychophysiological state of the brain, i.e. whether the brain was in a restful state or was activated by excessive stimulation. The restful state generated sharper and higher waveforms than the activated state. The suppression of the second PS0 response to the testing stimulus could also be explained as the results of brain activation by the first conditioning stimulus. These results also suggest that sensory attenuation may occur prior to the conditioning stimulus. We speculated that a more primary filtering mechanism might exist for sensory input prior to the gating mechanism suggested by Freedman et al. (1983). This initial filtering mechanism may depend upon the general state of the activation of the brain.
61. SINGLE-TRIAL PS0 IN NORMAL AND SCHIZOPHRENIC SUBJECTS Y. Jin, S.G. Potkin, J. Wu, C. Dang, & C. Sandman Department of Psychiatry, University of California Irvine Medical Center, Orange, CA 92668 Variation in the time latency between trials (jitter effects) might significantly reduce the amplitude and increase the latency of the averaged evoked potentials waveform. To address the methodology differently we calculated single trial P50's in 8 patients with schizophrenia and 6 normal subjects with a paired click (S !-$2) !)50 paradigm and compared them to averaged PS0's. Forty trials were collected and averaged for each subject. Schizophrenic patients showed a significantly lower amplitude of the !)50 response to the first conditioning click (SI: 3.9 4. 1.4) than normal controis (SI: 8.0 :t: 5.2, p<0.05). Gating ratio ($2/SI) was also different between patients (0.7 4. 0.4) and controls (0.3 + 0.1, p<0.05). By using a proper digital frequency filter, each single trial of the P50 responses w~ analyzed off-line. Results showed that the variation coefficients of the !)50 latencies were significantly different between SI (0.14 + 0.04) and $2(0.25 + 0.02) in normal subjects (p<0.01) but not in schizophrenic patients (SI: 0.25 + 0.04, $2:0.29 4- 0.04, p>O.05). The difference of the variation coefficient of S! latency was also significant between the two groups (lg0.001), while the variation of $2 remained the same (Ig0.05). As the jitter effect was removed from the analysis, there was no significant amplitude difference of either !)50 responses (S! & $2) between schizophrenic (SI: 12.7 + 3.3, $2:13.8 + 3.0) and normal subjects (St: 16.64.5.2,p<0.05; S2:15.0 4. 2.3,p<0.05). The difference of the gating ratio between the two groups also disappeared. These results suggested that the temporal variation of the I)50 response might play an important role in the sensory information processing.
62. NEONATAL HIPPOCAMPAL DAMAGE DISRUPTS SENSORIMOTOR GATING IN POSTPUBERTAL RATS B. K. Lipska i, N. R. Swerdiow 2, (3. E. Jaskiw 3, M. A. Geyer2, D. L. Braff2, & D. R. Weinberger I tNIMH, Neuroscience Center at St Elizabeths, Washington/3C 20032, 2USCD School of Medicine, La Jolla CA 92093, Dept. Psychiatry, VAMC Brecksville, OH 44141 Neonatal excitotoxic hippocampal damage in the rat results in postpubertal onset of a variety of abnormal behaviors related to excessive dopamin-
baseline startle amplitude, and since ALX does not reduce strychninepotentiated startle. The effects of alphaxalone on CRF-potentiated startle may not be generalized to all CRF-sfimulated behaviors, since alphaxalone failed to disrupt CRF-stimulated locomotor activity. CRF-potentiated startle is a useful assay for studying the effects of novel anxiolyfic agents, and alphaxalone appears to be a steroid anesthetic with anxiolytic properties in this assay.
59. SIMILAR EFFECTS OF STIMULANTS ON LATENT INHIBITION AND PREPULSE INHIBITION V.P. Bakshi, M.A. Geyer, N. Taaid, & N.R. Swerdlow Depts of Neuroscience and Psychiatry, UCSD School of Medicine, La Jolla, CA 92093-0804 Sensorimotor gating deficits characterize several neumpsychiatric disorders, including schizophrenia. Latent inhibition (LI) and prepulse inhibition (PPi) are used to study the neural subslxates underlying sensorimotor gating deficits, in LI, exposure to a stimulus retards the subsequent association of that stimulus with an event. In PPI, a subthreshold stimulus presented immediately prior to a startling stimulus inhibits or attenuates the startle response. Dopamine agnnists such as amphetamine disrupt both L! and PPi. Amphetamine has been reported to increase startle amplitude as well as exploratory locomotion. Such "non-specific" behavioral activation might complicate the interpretation of amphetamine-induced changes in PP! or LI. We compared the effects of three behaviorally activating drugs on LI and PPI. Separate groups of rats were treated with either vehicle, the dopamine releaser amphetamine (I .5 mg/kg, ip), the glycine antagnnist strychnine (0.75 mg/kg, ip), or the phosphodiesterase inhibitor caffeine (!0 mg/kg, sc), and then tested in either an active avoidance chamber (for LI) or startle chambers (for PPI). Locomotion was measured by inter-trial crossing in the avoidance chamber. As reported previously, amphetamine stimulated locomotion and disrupted both LI and PPi, but in this case did not elevate startle amplitude, in contrast, caffeine enhanced locomotion, but had no effect on LI or PPI. Strychnine produced only mild behavioral activation, significantly elevated startle amplitude, and significantly disrupted LI and PPI. These results suggest that neither increased startle amplitude nor locomotor activation are necessary or sufficient conditions for disruption of sensorimotor gating as measured by LI or PPI.
60. P50 RESPONSES IN NORMAL SUBJECTS WITH SENSORY OVERLOADING Y. Jin, S.G. Potkin, J. Wu, L. Tjahjono, & C. Sandman Department of Psychiatry, University of California Irvine Medical Center, Orange, CA 9266~ Schizophrenic patients have been reported to have a decreased sensory gating measured by high $2/SI ratio on the paired evoked potential (EP) responses. This study was proposed to develop a psychophysiological model of schizophrenia by sensory overloading. Conditioning-testing auditory PS0 EP was applied to 25 normal subjects (16 males and 9 females, age: 22.4 + 9.3). PS0 data for each subject was collected under two experimental conditions: a resting condition and a sensory overload condition. The sensory overload was produced by a series of random photic interferences. Consistent with the observation in schizophrenic patients, the ex-
B[OL PSYCHIATRY 631 1994,35:615-747
cessive sensory stimulation significantly attenuated the first conditioning !)50 response (p<0.001), while the second testing response was not changed (p-0.32). Consequently the C-T ratio was also significantly increased with the visual interference (p<0.05). These findings suggested that the amplitude of PS0, especially that to the first stimulus was dependent on the psychophysiological state of the brain, i.e. whether the brain was in a restful state or was activated by excessive stimulation. The restful state generated sharper and higher waveforms than the activated state. The suppression of the second PS0 response to the testing stimulus could also be explained as the results of brain activation by the first conditioning stimulus. These results also suggest that sensory attenuation may occur prior to the conditioning stimulus. We speculated that a more primary filtering mechanism might exist for sensory input prior to the gating mechanism suggested by Freedman et al. (1983). This initial filtering mechanism may depend upon the general state of the activation of the brain.
61. SINGLE-TRIAL PS0 IN NORMAL AND SCHIZOPHRENIC SUBJECTS Y. Jin, S.G. Potkin, J. Wu, C. Dang, & C. Sandman Department of Psychiatry, University of California Irvine Medical Center, Orange, CA 92668 Variation in the time latency between trials (jitter effects) might significantly reduce the amplitude and increase the latency of the averaged evoked potentials waveform. To address the methodology differently we calculated single trial P50's in 8 patients with schizophrenia and 6 normal subjects with a paired click (S !-$2) !)50 paradigm and compared them to averaged PS0's. Forty trials were collected and averaged for each subject. Schizophrenic patients showed a significantly lower amplitude of the !)50 response to the first conditioning click (SI: 3.9 4. 1.4) than normal controis (SI: 8.0 :t: 5.2, p<0.05). Gating ratio ($2/SI) was also different between patients (0.7 4. 0.4) and controls (0.3 + 0.1, p<0.05). By using a proper digital frequency filter, each single trial of the P50 responses w~ analyzed off-line. Results showed that the variation coefficients of the !)50 latencies were significantly different between SI (0.14 + 0.04) and $2(0.25 + 0.02) in normal subjects (p<0.01) but not in schizophrenic patients (SI: 0.25 + 0.04, $2:0.29 4- 0.04, p>O.05). The difference of the variation coefficient of S! latency was also significant between the two groups (lg0.001), while the variation of $2 remained the same (Ig0.05). As the jitter effect was removed from the analysis, there was no significant amplitude difference of either !)50 responses (S! & $2) between schizophrenic (SI: 12.7 + 3.3, $2:13.8 + 3.0) and normal subjects (St: 16.64.5.2,p<0.05; S2:15.0 4. 2.3,p<0.05). The difference of the gating ratio between the two groups also disappeared. These results suggested that the temporal variation of the I)50 response might play an important role in the sensory information processing.
62. NEONATAL HIPPOCAMPAL DAMAGE DISRUPTS SENSORIMOTOR GATING IN POSTPUBERTAL RATS B. K. Lipska i, N. R. Swerdiow 2, (3. E. Jaskiw 3, M. A. Geyer2, D. L. Braff2, & D. R. Weinberger I tNIMH, Neuroscience Center at St Elizabeths, Washington/3C 20032, 2USCD School of Medicine, La Jolla CA 92093, Dept. Psychiatry, VAMC Brecksville, OH 44141 Neonatal excitotoxic hippocampal damage in the rat results in postpubertal onset of a variety of abnormal behaviors related to excessive dopamin-