A mouse mutant strain highly resistant to methyl beta-carboline-3-carboxylate-induced seizures.

Abstract

The convulsant properties of methyl beta-carboline-3-carboxylate (beta-CCM) were evaluated in the TaT-fm/GncTa+/+Tfm strain carrying the tabby coat color (Ta) and/or the testicular feminization (Tfm) gene. When injected intraperitoneally within a 5-60 mg/kg dose range, beta-CCM-induced convulsions in less than 25% of the mice, thus providing evidence for a high resistance of this strain, as compared to classical strains of mice. However, this strain responds normally to the convulsant pentylenetetrazol (PTZ), suggesting a specific resistance to beta-CCM. Both the Ta gene and the TaTfm/Gnc genetic background were involved in the high resistance to beta-CCM. In addition, concentrations of neurosteroids and benzodiazepine binding, both modulating GABAA receptor efficacy, have been measured in order to elucidate the biological mechanisms of drug resistance.

• Authors: Y Clément, J M Launay, D Bondoux, P Venault, B Martin, J Young, P Robel, G Chapouthier
• Journal: Experimental brain research (Exp Brain Res) Vol. 110 Issue 1 Pg. 28-35 (Jun 1996) ISSN: 0014-4819 [Print] Germany
• PMID: 8817253 (Publication Type: Journal Article)

Chemical References

• Carbolines
• Convulsants
• Receptors, GABA-A
• pregnenolone sulfate
• Pregnenolone
• Pregnanolone
• beta-carboline-3-carboxylic acid methyl ester
• Pentylenetetrazole

Topics

• Animals
• Brain Chemistry (physiology)
• Carbolines
• Convulsants
• Drug Resistance (genetics)
• Evaluation Studies as Topic
• Female
• Male
• Mice
• Mice, Mutant Strains
• Pentylenetetrazole
• Pregnanolone (analysis)
• Pregnenolone (analysis)
• Radioligand Assay
• Receptors, GABA-A (analysis)
• Seizures (chemically induced, genetics)