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A QUANTITATIVE MICROIONTOPHORETIC ANALYSIS OF THE RESPONSES OF CENTRAL NEURONES TO NORADRENALINE: INTERACTIONS WITH COBALT, MANGANESE, VERAPAMIL AND DICHLOROISOPRENALINE
Author(s) -
FREEDMAN R.,
HOFFER B.J.,
WOODWARD D.J.
Publication year - 1975
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1975.tb07601.x
Subject(s) - verapamil , manganese , neuroscience , chemistry , cobalt , iontophoresis , medicine , psychology , calcium , organic chemistry , inorganic chemistry
1 A new experimental procedure has been devised for the study of pharmacological antagonism in the central nervous system using automated microiontophoresis to deliver pulses of agonists and computer‐generated histograms to quantify the neuronal response. The system allows study of potential antagonists having direct depressant effects and also of neurones with irregular or slow discharge rates. 2 The histogram analysis reveals the necessity for regular, periodic delivery of agonists during the assessment of agonist‐antagonist interactions. Without regular repetitive delivery, many agonists, such as noradrenaline, exhibit an apparent but artifactual decrease in inhibitory potency after an interruption of agonist pulses. Examples of this phenomenon are shown, using cerebellar Punkinje cells and cerebral cortical neurones in rats anaesthetized with halothane. 3 Preliminary results with these computer‐generated drug response histograms revealed manganese, cobalt, and verapamil to be generally ineffective as antagonists of noradrenaline, despite their direct depressant effects. 4 Conversely, dichloroisoprenaline (DCI), a β‐adrenoceptor antagonist, was effective in blocking noradrenaline‐induced depressions of firing in the cerebral cortex at doses which caused over 50% decrease in spontaneous discharge.