Effects of acute and chronic clozapine on d-amphetamine-induced disruption of auditory gating in the rat

Joy, Brian; McMahon, Robert P.; Shepard, Paul D.

doi:10.1007/s00213-003-1731-4

Cited by 10 publications

(6 citation statements)

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“…In the present study, we report behavioral as well as electrophysiological observations following sensory stimulation before and after several doses of the psychostimulant MPD. Most of the electrophysiological experiments investigating the property of MPD have been conducted in the presence of anesthesia [ 4 , 31 , 32 ], which is known to modulate CNS activity [ 33 ], or used brain slices [ 34 - 38 ] to record the effect of the drug on spontaneous activity and the role of different neurotransmitters in MPD action. None of the studies investigate, in freely behaving animals previously implanted with permanent electrodes and without the interference of anesthesia, the dose-response characteristics on sensory input recorded simultaneously from sites where psychostimulants are known to initiate and/or express their effects.…”

Section: Discussionmentioning

confidence: 99%

“…However, few studies have investigated the neurophysiological properties of psychostimulants, such as MPD, in intact humans or animals [ 30 ], especially its behavioral effects and alteration of sensory evoked neuronal activity in brain regions that are involved in the mesocorticolimbic DA system. Most neurophysiological studies that investigated psychostimulants have been conducted in vivo in the presence of anesthesia [ 4 , 31 , 32 ], which is known to interfere with CNS activity [ 33 ], or obtained in vitro on brain slices [ 34 - 38 ]. A valuable method to studying the mechanistic action of psychostimulants, such as MPD, on neuronal population is to record neuronal activity before and after administration of the psychostimulant in an intact, non-anesthetized, freely behaving subject through sensory-evoked field responses following sensory stimulation.…”

Section: Introductionmentioning

confidence: 99%

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Dose-response characteristics of methylphenidate on locomotor behavior and on sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats

Peng

Swann²,

Dafny

2006

Behav Brain Funct

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BackgroundMethylphenidate (MPD) is a psychostimulant commonly prescribed for attention deficit/hyperactivity disorder. The mode of action of the brain circuitry responsible for initiating the animals' behavior in response to psychostimulants is not well understood. There is some evidence that psychostimulants activate the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC).MethodsThe present study was designed to investigate the acute dose-response of MPD (0.6, 2.5, and 10.0 mg/kg) on locomotor behavior and sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats previously implanted with permanent electrodes. For locomotor behavior, adult male Wistar-Kyoto (WKY; n = 39) rats were given saline on experimental day 1 and either saline or an acute injection of MPD (0.6, 2.5, or 10.0 mg/kg, i.p.) on experimental day 2. Locomotor activity was recorded for 2-h post injection on both days using an automated, computerized activity monitoring system. Electrophysiological recordings were also performed in the adult male WKY rats (n = 10). Five to seven days after the rats had recovered from the implantation of electrodes, each rat was placed in a sound-insulated, electrophysiological test chamber where its sensory evoked field potentials were recorded before and after saline and 0.6, 2.5, and 10.0 mg/kg MPD injection. Time interval between injections was 90 min.ResultsResults showed an increase in locomotion with dose-response characteristics, while a dose-response decrease in amplitude of the components of sensory evoked field responses of the VTA, NAc, and PFC neurons. For example, the P3 component of the sensory evoked field response of the VTA decreased by 19.8% ± 7.4% from baseline after treatment of 0.6 mg/kg MPD, 37.8% ± 5.9% after 2.5 mg/kg MPD, and 56.5% ± 3.9% after 10 mg/kg MPD. Greater attenuation from baseline was observed in the NAc and PFC. Differences in the intensity of MPD-induced attenuation were also found among these brain areas.ConclusionThese results suggest that an acute treatment of MPD produces electrophysiologically detectable alterations at the neuronal level, as well as observable, behavioral responses. The present study is the first to investigate the acute dose-response effects of MPD on behavior in terms of locomotor activity and in the brain involving the sensory inputs of VTA, NAc, and PFC neurons in intact, non-anesthetized, freely behaving rats previously implanted with permanent electrodes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dose-response characteristics of methylphenidate on locomotor behavior and on sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats

Peng

Swann²,

Dafny

2006

Behav Brain Funct

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“… 65 , 76 Higher doses of clozapine, however, may improve gating by both decreasing S2 and increasing S1 amplitudes. 65 , 75 , 76 Human studies have mostly reported S1 increases after clozapine administration (Becker et al ; 80 Light et al; 133 Nagamoto et al ; 78 Nagamoto et al 79 ) although one study found that the drug decreased S2 amplitude (Adler et al 74 ).…”

Section: Hippocampal Gating As a Translational Tool: A Review And Evamentioning

confidence: 99%

Translational utility of rodent hippocampal auditory gating in schizophrenia research: a review and evaluation

et al. 2015

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Impaired gating of the auditory evoked P50 potential is one of the most pharmacologically well-characterized features of schizophrenia. This deficit is most commonly modeled in rodents by implanted electrode recordings from the hippocampus of the rodent analog of the P50, the P20–N40. The validity and effectiveness of this tool, however, has not been systematically reviewed. Here, we summarize findings from studies that have examined the effects of pharmacologic modulation on gating of the rodent hippocampal P20–N40 and the human P50. We show that drug effects on the P20–N40 are highly predictive of human effects across similar dose ranges. Furthermore, mental status (for example, anesthetized vs alert) does not appear to diminish the predictive capacity of these recordings. We then discuss hypothesized neuropharmacologic mechanisms that may underlie gating effects for each drug studied. Overall, this review supports continued use of hippocampal P20–N40 gating as a translational tool for schizophrenia research.

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“…In rodents, as in humans, sensory gating is usually measured as the ratio of the response amplitude to the first compared to the second stimulus (S2/S1). This ratio is often impaired in pharmacological models of schizophrenia targeting dopaminergic [43, 48–51] and glutamatergic [38, 51] systems, with many studies suggesting that the increased ratio is due to a decreased S1 response [49–51]. Although sensory gating has been tested in pharmacological animal models of schizophrenia, to our knowledge it has not been examined in NVHL rats.…”

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confidence: 99%

Auditory Sensory Gating in the Neonatal Ventral Hippocampal Lesion Model of Schizophrenia

et al. 2009

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Background/Aims: The neonatal ventral hippocampal lesion (NVHL) rat model shows biological and behavioral abnormalities similar to schizophrenia. Disturbed sensory gating reflects a consistent neurobiological abnormality in schizophrenia. Although of critical interest, sensory gating has not been evaluated in the NVHL model. Methods: The N40 rat analog of the human P50 was measured to assess sensory response and gating in NVHL and sham rats. Epidural electrodes recorded evoked potentials (EPs), from which amplitudes, latencies, difference scores (S1–S2) and gating ratios (S2/S1) were assessed. Power and phase locking were computed for evoked EEG activity, to test for frequency-specific abnormalities. Results: Prolonged S1 N40 latency was detected in the NVHL group, but amplitude and power measures did not differ. NVHL rats demonstrated disturbed phase-locked sensory gating at theta and beta frequencies, as well as reduced phase-locked gamma activity across stimuli, most robustly at S1. Conclusions: While measures of sensory gating obtained from the EP were relatively insensitive to the NVHL model, phase locking across trials was affected. NVHL rats may have increased evoked response temporal variability, similar to patients with schizophrenia. This pattern of findings likely reflects core developmental NVHL disturbances in dorsal hippocampal circuits associated with temporal and frontal areas.

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Effects of acute and chronic clozapine on d-amphetamine-induced disruption of auditory gating in the rat

Abstract: Qualitative differences between the idiopathic gating deficits observed in schizophrenic patients and AMPH-induced increases in T/C ratio in animals limit this models utility as a means of evaluating the ability of atypical antipsychotic drugs to restore normal sensory gating.

Cited by 10 publications

References 50 publications

Dose-response characteristics of methylphenidate on locomotor behavior and on sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats

Dose-response characteristics of methylphenidate on locomotor behavior and on sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats

Translational utility of rodent hippocampal auditory gating in schizophrenia research: a review and evaluation

Auditory Sensory Gating in the Neonatal Ventral Hippocampal Lesion Model of Schizophrenia

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