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The effects of d-amphetamine, methylphenidate, sydnocarb, and caffeine on prepulse inhibition of the startle reflex in DBA/2 mice

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Abstract

Rationale

Dopamine (DA) agonists decrease prepulse inhibition (PPI) and are widely used in translational models for the sensorimotor gating deficits in schizophrenia. Reductions in PPI induced by DA agonists are routinely reversed by antipsychotics in these translational models. Nevertheless, under conditions of low-baseline PPI, DA agonists may increase PPI in humans and experimental animals. DBA/2 mice have naturally low-baseline PPI, which as in the drug-induced translational models, is increased by antipsychotics.

Objective

Determine whether DBA/2 mice respond like other models of low-baseline PPI by evaluating the effect of psychostimulants (caffeine, 30–100 mg/kg IP) and the indirect DA agonists d-amphetamine (0.3–10 mg/kg IP), methylphenidate (10–100 mg/kg IP), and sydnocarb (10–30 mg/kg IP), a selective DA transporter inhibitor on PPI. Furthermore, baseline PPI in DBA/2 mice was increased by noise exposure and the effect of d-amphetamine was assessed.

Results

PPI was increased at one dose for each of the psychostimulants when baseline PPI was low in naïve DBA/2 mice. Effective doses were 3 mg/kg of d-amphetamine, 30 mg/kg of methylphenidate, 30 mg/kg of sydnocarb, and 100 mg/kg of caffeine. Higher doses of d-amphetamine (10 mg/kg) and methylphenidate (100 mg/kg IP) decreased PPI. When the baseline PPI was increased by noise exposure, 10 mg/kg of d-amphetamine only reduced PPI.

Conclusion

Lower doses of psychostimulants increased PPI in naïve DBA/2 mice in a manner consistent with their naturally low-baseline PPI, and higher doses decreased PPI, consistent with effects observed in most mouse strains.

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Acknowledgements

Cephalon, Inc. employs the authors and sponsored this research. Cephalon, Inc. has no proprietary interest in the drugs used in these studies. The experiments described in this manuscript comply with the current laws of the United States, the country in which they were performed.

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  1. Michael J. Marino

    Present address: Merck and Co., 770 Sumneytown Pike, West Point, PA, 19486, USA

Authors and Affiliations

  1. CNS Biology, Worldwide Discovery Research, Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA, 19380, USA

    Dorothy G. Flood, Eva Zuvich, Michael J. Marino & Maciej Gasior

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  1. Dorothy G. Flood
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Correspondence to Dorothy G. Flood.

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Flood, D.G., Zuvich, E., Marino, M.J. et al. The effects of d-amphetamine, methylphenidate, sydnocarb, and caffeine on prepulse inhibition of the startle reflex in DBA/2 mice. Psychopharmacology 211, 325–336 (2010). https://doi.org/10.1007/s00213-010-1901-0

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  • DOI: https://doi.org/10.1007/s00213-010-1901-0

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