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Research ArticleNeuropharmacology

Long-Lasting Attenuation of Amygdala-Kindled Seizures after Convection-Enhanced Delivery of Botulinum Neurotoxins A and B into the Amygdala in Rats

Maciej Gasior, Rebecca Tang and Michael A. Rogawski
Journal of Pharmacology and Experimental Therapeutics September 2013, 346 (3) 528-534; DOI: https://doi.org/10.1124/jpet.113.205070
Maciej Gasior
Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (M.G., R.T., M.A.R.); and Department of Neurology, School of Medicine, University of California, Davis, Sacramento, California (M.A.R.)
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Rebecca Tang
Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (M.G., R.T., M.A.R.); and Department of Neurology, School of Medicine, University of California, Davis, Sacramento, California (M.A.R.)
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Michael A. Rogawski
Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland (M.G., R.T., M.A.R.); and Department of Neurology, School of Medicine, University of California, Davis, Sacramento, California (M.A.R.)
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Abstract

Botulinum neurotoxins (BoNTs) are well recognized to cause potent, selective, and long-lasting neuroparalytic actions by blocking cholinergic neurotransmission to muscles and glands. There is evidence that BoNT isoforms can also inhibit neurotransmission in the brain. In this study, we examined whether locally delivered BoNT/A and BoNT/B can attenuate kindling measures in amygdala-kindled rats. Male rats were implanted with a combination infusion cannula–stimulating electrode assembly into the right basolateral amygdala. Fully kindled animals received a single infusion of vehicle or BoNT/A or BoNT/B at doses of 1, 3.2, or 10 ng over a 20-minute period by convection-enhanced delivery. Electrographic (EEG) and behavioral kindling measures were determined at selected times during the 3- to 64-day period after the infusion. BoNT/B produced a dose-dependent elevation in after-discharge threshold and duration and a reduction in the seizure stage and duration of behavioral seizures that lasted for up to 50 days after infusion. BoNT/A had similar effects on EEG measures; behavioral seizure measures were also reduced, but the effect did not reach statistical significance. The effects of both toxins on EEG and behavioral measures progressively resolved during the latter half of the observation period. Animals gained weight normally, maintained normal body temperature, and did not show altered behavior. This study demonstrates for the first time that locally delivered BoNTs can produce prolonged inhibition of brain excitability, indicating that they could be useful for the treatment of brain disorders, including epilepsy, that would benefit from long-lasting suppression of neurotransmission within a circumscribed brain region.

Footnotes

    • Received March 23, 2013.
    • Accepted June 12, 2013.
  • ↵1 Current affiliation: Discovery Medicine, Neuroscience, Bristol-Myers Squibb, Princeton, New Jersey.

  • ↵2 Current affiliation: Virginia Commonwealth University Medical Center, Richmond, Virginia.

  • This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grants NS002877, NS072094, NS079202]; and the Intramural Research Program of the National Institutes of Health [National Institute of Neurological Disorders and Stroke].

  • dx.doi.org/10.1124/jpet.113.205070.

  • U.S. Government work not protected by U.S. copyright
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Journal of Pharmacology and Experimental Therapeutics: 346 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 346, Issue 3
1 Sep 2013
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Research ArticleNeuropharmacology

CED of BoNTs in Amygdala Kindling

Maciej Gasior, Rebecca Tang and Michael A. Rogawski
Journal of Pharmacology and Experimental Therapeutics September 1, 2013, 346 (3) 528-534; DOI: https://doi.org/10.1124/jpet.113.205070

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Research ArticleNeuropharmacology

CED of BoNTs in Amygdala Kindling

Maciej Gasior, Rebecca Tang and Michael A. Rogawski
Journal of Pharmacology and Experimental Therapeutics September 1, 2013, 346 (3) 528-534; DOI: https://doi.org/10.1124/jpet.113.205070
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