Calcium channel activation and self-biting in mice.
The L type calcium channel agonist (+/-)Bay K 8644 has been reported to cause characteristic motor abnormalities in adult mice. The current study shows that administration of this drug can also cause the unusual phenomenon of self-injurious biting, particularly when given to young mice. Self-biting is provoked by injecting small quantities of (+/-)Bay K 8644 directly into the lateral ventricle of the brain, suggesting a central effect of the drug. Similar behaviors can be provoked by administration of another L type calcium channel agonist, FPL 64176. The self-biting provoked by (+/-)Bay K 8644 can be inhibited by pretreating the mice with dihydropyridine L type calcium channel antagonists such as nifedipine, nimodipine, or nitrendipine. However, self-biting is not inhibited by nondihydropyridine antagonists including diltiazem, flunarizine, or verapamil. The known actions of (+/-)Bay K 8644 as an L type calcium channel agonist, the reproduction of similar behavior with another L type calcium channel agonist, and the protection afforded by certain L type calcium channel antagonists implicate calcium channels in the mediation of the self-biting behavior. This phenomenon provides a model for studying the neurobiology of this unusual behavior.
Jinnah
H A
HA
Department of Neurology, Johns Hopkins Hospital, Baltimore, MD 21287, USA. hjinnah@welch.jhu.edu
Yitta
S
S
Drew
T
T
Kim
B S
BS
Visser
J E
JE
Rothstein
J D
JD
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000009:adverse effects*; D000374:Aggression / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001733:Bites and Stings; D002120:Calcium Channel Agonists / Q000009:adverse effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D004095:Dihydropyridines / Q000737:chemistry; D004110:Diltiazem / Q000494:pharmacology; D015640:Ion Channel Gating; D051379:Mice; D008810:Mice, Inbred C57BL; D009543:Nifedipine / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D011758:Pyrroles / Q000009:adverse effects; D016728:Self-Injurious Behavior / Q000139:chemically induced*
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D011758:Pyrroles; C071658:FPL 64176; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D009568:Nitrendipine; D004110:Diltiazem; D009543:Nifedipine