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Chronic cocaine intoxication alters hippocampal sodium channel function
J Zhai1, S J Wieland, F M Sessler
1Department of Neurobiology and Anatomy, MCP/Hahnemann School of Medicine, Allegheny University of the Health Sciences, Philadelphia, PA 19129, USA.
Neuroscience Letters
|June 27, 1997
Summary
Repeated cocaine exposure increases seizure susceptibility. This study found that cocaine alters sodium channels in rat hippocampal neurons, enhancing their excitability and contributing to increased seizure risk.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Repeated subconvulsive cocaine administration increases seizure susceptibility and lethality.
- The underlying mechanisms of this heightened cocaine-induced seizure response remain unclear.
Purpose of the Study:
- To investigate functional changes in voltage-dependent sodium (Na+) channels in rat hippocampal CA1 pyramidal neurons following repeated subconvulsive cocaine exposure.
Main Methods:
- Whole cell patch-clamp recordings were performed on acutely dissociated hippocampal neurons from rats previously injected with subconvulsive doses of cocaine (45 mg/kg/day, i.p.) for 5-6 days.
- In vitro electrophysiological recordings were used to assess Na+ channel function.
Main Results:
- Neurons from cocaine-treated rats exhibited augmented peak Na+ currents.
- A depolarizing shift in the steady-state inactivation of Na+ channels was observed.
- These alterations increase the availability of Na+ channels, potentially enhancing neuronal excitability.
Conclusions:
- Functional changes in voltage-dependent Na+ channels, specifically increased peak currents and altered inactivation properties, occur after repeated subconvulsive cocaine administration.
- These channel modifications may enhance CA1 pyramidal neuron excitability, contributing to the observed increase in cocaine-induced seizure responsiveness.