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Lorazepam attenuates the behavioral effects of dizocilpine
J M Fahey1, G A Pritchard, J S Pratt
1Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.
Pharmacology, Biochemistry, and Behavior
|February 11, 1999
Summary
This study investigated how dizocilpine and CPP affect lorazepam
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Understanding the interplay between excitatory and inhibitory neurotransmitter systems is crucial for developing effective neurological treatments.
- Dizocilpine (an NMDA receptor antagonist) and CPP (an AMPA/kainate receptor antagonist) modulate excitatory neurotransmission.
- Lorazepam, a benzodiazepine, enhances inhibitory neurotransmission via GABA-A receptors.
Purpose of the Study:
- To characterize the interaction between excitatory (dizocilpine, CPP) and inhibitory (lorazepam) neurotransmitter systems.
- To evaluate the effects of these agents on open-field behavior and pentylenetetrazol-induced seizures in mice.
Main Methods:
- Mice were administered dizocilpine, CPP, or vehicle before lorazepam or vehicle.
- Open-field behavior (locomotion, rearing, stereotypy) was monitored.
- Pentylenetetrazol-induced seizures were assessed via intravenous infusion.
Main Results:
- Dizocilpine increased locomotor activity and stereotypy; lorazepam decreased activity and antagonized dizocilpine-induced hyperactivity.
- Lorazepam exhibited dose-dependent anticonvulsant effects against pentylenetetrazol-induced seizures.
- CPP reduced rearing and stereotypy but did not affect seizure threshold or lorazepam's anticonvulsant activity.
Conclusions:
- Lorazepam's antagonism of dizocilpine-induced hyperactivity suggests an interaction in dopaminergic tone regulation.
- The findings highlight lorazepam's efficacy as an anticonvulsant, independent of NMDA or AMPA/kainate receptor modulation.
- This research provides insights into the complex interactions between different neurotransmitter systems in modulating behavior and seizure susceptibility.
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