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The antiepileptic drug levetiracetam improves auditory gating in DBA/2 mice.

Smucny J, Stevens KE, Tregellas JR - NPJ Schizophr (2015)

Bottom Line: Gating effects were evaluated using four doses of LEV (3, 10, 30, and 100 mg/kg).The 10 mg/kg dose improved P20-N40 gating (P = 0.016).No other doses significantly affected gating.

View Article: PubMed Central - HTML - PubMed

Affiliation: Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA ; Research Service, Denver VA Medical Center, Denver, CO, USA ; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

ABSTRACT

Schizophrenia is associated with deficits in P50 gating. This deficit is preclinically modeled in the DBA/2 mouse by depth recordings in the hippocampus. Neurobiologically, the deficit may be due to dysfunction in inhibitory circuitry. It follows that anti-epileptic drugs which impact this circuitry, such as levetiracetam (LEV), may improve gating. To that end, the goal of this study was to evaluate the ability of LEV to normalize sensory gating in the DBA/2 mouse. Gating of the murine analog of the P50, the P20-N40, was evaluated from in vivo hippocampal recordings in 39 male DBA/2 mice. Gating effects were evaluated using four doses of LEV (3, 10, 30, and 100 mg/kg). The 10 mg/kg dose improved P20-N40 gating (P = 0.016). No other doses significantly affected gating. Low-dose LEV may improve P20-N40 gating in the DBA/2 mouse model of schizophrenia. Low-doses of LEV may improve P20-N40 gating in the DBA/2 mouse model of schizophrenia and warrant further investigation in the illness.

No MeSH data available.


Related in: MedlinePlus

Representative waveforms demonstrating the effect of LEV (10 mg/kg) on P20-N40 gating in DBA/2 mice. Waveforms on the left side represent pre-drug (i.e., baseline) responses to the first (S1) and second (S2) stimuli. Waveforms on the right side represent post-drug responses to the first and second stimuli. Burst response artifacts represent the auditory stimuli, and tic marks denote the P20-N40 auditory-evoked potentials. In these representative examples, injection of LEV alone reduced S2/S1 ratio relative to baseline by increasing S1 amplitude while not affecting S2 amplitude. LEV, levetiracetam.
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Figure 2: Representative waveforms demonstrating the effect of LEV (10 mg/kg) on P20-N40 gating in DBA/2 mice. Waveforms on the left side represent pre-drug (i.e., baseline) responses to the first (S1) and second (S2) stimuli. Waveforms on the right side represent post-drug responses to the first and second stimuli. Burst response artifacts represent the auditory stimuli, and tic marks denote the P20-N40 auditory-evoked potentials. In these representative examples, injection of LEV alone reduced S2/S1 ratio relative to baseline by increasing S1 amplitude while not affecting S2 amplitude. LEV, levetiracetam.

Mentions: For S2/S1 ratio, a significant main effect of time was observed for the 10 mg/kg dose (F(17,153) = 1.98, P = 0.016). This dose decreased S2/S1 ratio relative to baseline (Figures 1c,f and 2).


The antiepileptic drug levetiracetam improves auditory gating in DBA/2 mice.

Smucny J, Stevens KE, Tregellas JR - NPJ Schizophr (2015)

Representative waveforms demonstrating the effect of LEV (10 mg/kg) on P20-N40 gating in DBA/2 mice. Waveforms on the left side represent pre-drug (i.e., baseline) responses to the first (S1) and second (S2) stimuli. Waveforms on the right side represent post-drug responses to the first and second stimuli. Burst response artifacts represent the auditory stimuli, and tic marks denote the P20-N40 auditory-evoked potentials. In these representative examples, injection of LEV alone reduced S2/S1 ratio relative to baseline by increasing S1 amplitude while not affecting S2 amplitude. LEV, levetiracetam.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4548960&req=5

Figure 2: Representative waveforms demonstrating the effect of LEV (10 mg/kg) on P20-N40 gating in DBA/2 mice. Waveforms on the left side represent pre-drug (i.e., baseline) responses to the first (S1) and second (S2) stimuli. Waveforms on the right side represent post-drug responses to the first and second stimuli. Burst response artifacts represent the auditory stimuli, and tic marks denote the P20-N40 auditory-evoked potentials. In these representative examples, injection of LEV alone reduced S2/S1 ratio relative to baseline by increasing S1 amplitude while not affecting S2 amplitude. LEV, levetiracetam.
Mentions: For S2/S1 ratio, a significant main effect of time was observed for the 10 mg/kg dose (F(17,153) = 1.98, P = 0.016). This dose decreased S2/S1 ratio relative to baseline (Figures 1c,f and 2).

Bottom Line: Gating effects were evaluated using four doses of LEV (3, 10, 30, and 100 mg/kg).The 10 mg/kg dose improved P20-N40 gating (P = 0.016).No other doses significantly affected gating.

View Article: PubMed Central - HTML - PubMed

Affiliation: Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA ; Research Service, Denver VA Medical Center, Denver, CO, USA ; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

ABSTRACT

Schizophrenia is associated with deficits in P50 gating. This deficit is preclinically modeled in the DBA/2 mouse by depth recordings in the hippocampus. Neurobiologically, the deficit may be due to dysfunction in inhibitory circuitry. It follows that anti-epileptic drugs which impact this circuitry, such as levetiracetam (LEV), may improve gating. To that end, the goal of this study was to evaluate the ability of LEV to normalize sensory gating in the DBA/2 mouse. Gating of the murine analog of the P50, the P20-N40, was evaluated from in vivo hippocampal recordings in 39 male DBA/2 mice. Gating effects were evaluated using four doses of LEV (3, 10, 30, and 100 mg/kg). The 10 mg/kg dose improved P20-N40 gating (P = 0.016). No other doses significantly affected gating. Low-dose LEV may improve P20-N40 gating in the DBA/2 mouse model of schizophrenia. Low-doses of LEV may improve P20-N40 gating in the DBA/2 mouse model of schizophrenia and warrant further investigation in the illness.

No MeSH data available.


Related in: MedlinePlus