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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

(a–c) Effect of increasing doses of LEV (3, 10, 30, and 100 mg/kg, i.p.) on S1 response amplitudes (a), S2 response amplitudes (b), and S2/S1 ratios (c) as a function of time in DBA/2 mice. The first six points (−30, −25, etc.) refer to the baseline period of recording, before administration of drug(s). The last 12 points (0, 5, 10, etc.) refer to the post-drug administration period of recording. Asterisks mark those post-drug time points at which the S1 or S2 amplitude is significantly different from the average of the baseline S1 or S2 amplitudes, as determined using Fisher’s LSD (*P<0.05, **P<0.01). Data are mean ± s.e.m. (d–e) Average baseline and post-drug S1 amplitude (d), S2 amplitude (e), and S2/S1 ratio (f) for each LEV dose. Data are mean ±s.e.m. LEV, levetiracetam; LSD, least significant difference.
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Figure 1: (a–c) Effect of increasing doses of LEV (3, 10, 30, and 100 mg/kg, i.p.) on S1 response amplitudes (a), S2 response amplitudes (b), and S2/S1 ratios (c) as a function of time in DBA/2 mice. The first six points (−30, −25, etc.) refer to the baseline period of recording, before administration of drug(s). The last 12 points (0, 5, 10, etc.) refer to the post-drug administration period of recording. Asterisks mark those post-drug time points at which the S1 or S2 amplitude is significantly different from the average of the baseline S1 or S2 amplitudes, as determined using Fisher’s LSD (*P<0.05, **P<0.01). Data are mean ± s.e.m. (d–e) Average baseline and post-drug S1 amplitude (d), S2 amplitude (e), and S2/S1 ratio (f) for each LEV dose. Data are mean ±s.e.m. LEV, levetiracetam; LSD, least significant difference.

Mentions: Consistent with previous studies, DBA/2 mice failed to suppress S2 amplitudes during baseline as evidenced by mean S2/S1 ratios of approximately 1 (Figure 1c,f).


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

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

(a–c) Effect of increasing doses of LEV (3, 10, 30, and 100 mg/kg, i.p.) on S1 response amplitudes (a), S2 response amplitudes (b), and S2/S1 ratios (c) as a function of time in DBA/2 mice. The first six points (−30, −25, etc.) refer to the baseline period of recording, before administration of drug(s). The last 12 points (0, 5, 10, etc.) refer to the post-drug administration period of recording. Asterisks mark those post-drug time points at which the S1 or S2 amplitude is significantly different from the average of the baseline S1 or S2 amplitudes, as determined using Fisher’s LSD (*P<0.05, **P<0.01). Data are mean ± s.e.m. (d–e) Average baseline and post-drug S1 amplitude (d), S2 amplitude (e), and S2/S1 ratio (f) for each LEV dose. Data are mean ±s.e.m. LEV, levetiracetam; LSD, least significant difference.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4548960&req=5

Figure 1: (a–c) Effect of increasing doses of LEV (3, 10, 30, and 100 mg/kg, i.p.) on S1 response amplitudes (a), S2 response amplitudes (b), and S2/S1 ratios (c) as a function of time in DBA/2 mice. The first six points (−30, −25, etc.) refer to the baseline period of recording, before administration of drug(s). The last 12 points (0, 5, 10, etc.) refer to the post-drug administration period of recording. Asterisks mark those post-drug time points at which the S1 or S2 amplitude is significantly different from the average of the baseline S1 or S2 amplitudes, as determined using Fisher’s LSD (*P<0.05, **P<0.01). Data are mean ± s.e.m. (d–e) Average baseline and post-drug S1 amplitude (d), S2 amplitude (e), and S2/S1 ratio (f) for each LEV dose. Data are mean ±s.e.m. LEV, levetiracetam; LSD, least significant difference.
Mentions: Consistent with previous studies, DBA/2 mice failed to suppress S2 amplitudes during baseline as evidenced by mean S2/S1 ratios of approximately 1 (Figure 1c,f).

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