Further characterization of the neurofunctional effects of the calcium ionophore A23187.
Calimycin (A23187), a divalent cationic ionophore which increases intraneuronal concentrations of calcium, has been shown to produce neurofunctional changes associated with depression of brain excitability. The present report describes further characterization of the neurofunctional effects of acute parenteral exposure to A23187. Adult male rats were tested for the effects of A23187 on operant performance and general motor activity. In order to gain some insight into the neuronal systems which may be affected by A23187, brain levels of norepinephrine (NE), dopamine, serotonin, and their metabolites were determined. In addition, provocative pharmacologic challenges were employed to assess the interaction between A23187 and the centrally active drugs amphetamine (AMPH), scopolamine (SCOP), or chlorpromazine (CPZ). A23187 was found to effectively suppress fixed ratio-15 operant performance (p less than 0.001) at a dose of 0.5 mg/kg. This effect was temporary in nature inasmuch as performance was normalized by the day after dosing. This same dose of A23187, which produces a selective hypomotility, was found to have no apparent latent effects on the processes controlling circadian motor activity. Neurochemically, A23187 at 1 mg/kg induced a 64% increase (p less than 0.01) in the NE metabolite 3-methoxy-4-hydroxyphenylglycol, although levels of NE were unaffected. In the pharmacological challenge studies, AMPH and SCOP both attenuated and CPZ enhanced the acute hypomotility induced by 0.5 mg A23187/kg. The data show that low doses of A23187 induce a specific pattern of neurobehavioral dysfunction which may involve some interaction between the central catecholaminergic and cholinergic systems.
Sobotka
T
T
Division of Toxicology, Food and Drug Administration, Washington, D.C. 20204.
Brodie
R
R
Quander
Y
Y
O'Donnell
M
M
West
G
G
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012055:Reinforcement Schedule
D002395:Catecholamines; D000001:Calcimycin