Neuroscience 2002 Abstract
| Presentation Number: | 136.8 |
|---|---|
| Abstract Title: | SEIZURE AND STRAUB TAIL RESPONSES IN KNOCK-IN MICE CARRYING HYPERSENSITIVE NEURONAL NICOTINIC RECEPTORS. |
| Authors: |
Fonck, C. I.*1
; Nashmi, R.1
; Labarca, C.1
; Deshpande, P.1
; Lester, H. A.1
1Division of Biology, California Institute of Technology, Pasadena, CA |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Ligand Gated Ion Channels -- Nicotinic acetylcholine receptors |
| Secondary Theme and Topics | Neurological and Psychiatric Conditions<br />- Epilepsy<br />-- Human studies and animal models |
| Session: |
136. Ligand gated ion channels: nicotinic acetylcholine receptors--nicotine behavior and physiology Poster |
| Presentation Time: | Sunday, November 3, 2002 4:00 PM-5:00 PM |
| Location: | Hall A2-B3 C-20 |
| Keywords: | ADNFLE, ACETYLCHOLINE, ACETYLCHOLINESTERASE, EPIBATIDINE |
We studied knock-in mice with a gain of function Leu9’Ser mutation in the M2 region of the nicotinic acetylcholine receptor (nAChR) α4 subunit. We previously showed that heterozygous L9’S mice (hets) are ~ 10 times more sensitive to nicotine-induced seizures than their wild type littermates (WT) (Fonck et al, SFN, 2001). Seizure studies on α4-mutated mice may be interesting for epilepsy research because all known mutations responsible for autosomal dominant nocturnal frontal lobe epilepsy occur in the M2 region of the α4 or β2 subunits. Hets and WT received a single injection of either: a) the nicotinic agonist epibatidine, b) the cholinesterase inhibitor and nicotinic modulator galanthamine or c) the cholinesterase inhibitor tacrine. Hets were significantly more sensitive than WT to epibatidine, galanthamine and tacrine as assessed by latency to seizure and Straub tail. Epibatidine (2 to 10 μg/kg), galanthamine (5 to 20 mg/kg) and tacrine (5 to 20 mg/kg) induced seizures and Straub tail in hets in a dose dependent manner, while no noticeable effects were seen in WT at the lower concentrations used. Seizures in mutant animals were always preceded by Straub tail, and at doses of 2 μg/kg, 5 mg/kg and 5 mg/kg for each drug respectively, mice displayed Straub tail but no seizure. These results suggest that direct as well as indirect cholinergic stimulation can induce seizures in L9’S mice. Gain of function mice may be useful in testing drugs targeted to specific neurotransmitter systems in the brain. Supported by: TRDRP, NS-117656, MH-49176.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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