Penicillin iontophoresis and the responses of somatosensory cortical neurons to amino acids

Abstract

In low doses (<100 nA) penicillin iontophoresis resulted in enhanced physiologic responses (EPRs) to mechanical or electrical contralateral upper extremity skin stimulation. γ-Aminobutyric acid (GABA) antagonism could be detected as a subtle shift in the log dose-response curve at a penicillin dose of 100 nA applied for 10–20 min. Such antagonism was not consistently detectable below this dose, although the EPR was readily demonstrable at lower penicillin doses (20–40 nA) applied for 1–2 min. In moderate doses (100–600 nA) penicillin iontophoresis produced enhanced neuronal firing rates in the majority of units. At these same doses of penicillin weak, non-specific, and reversible antagonism of responses to inhibitory amino acids was demonstrated in the inverse order of potency l-glycine (GLY) > β-alanine (ALA) > GABA. The excitatory effects of d,l-homocysteic acid (HC) or l-glutamate (GLU) were not significantly potentiated by comparable penicillin doses (200–400 nA), suggesting against postsynaptic hypersensitivity to these excitatory agents. In higher doses (700 nA−2 μA) penicillin iontophoresis induced the gradual onset of initially negative electrocorticogram (ECoG) discharges. These were seen first in the depth and then surface ECoG with gradually increasing amplitude depending on the dose and duration of iontophoresis. A non-specific decreased response to inhibitory amino acids was observed prior to the onset of unit bursting or depth ECoG discharges. GABA log dose-response curves obtained during modernate and high dose penicillin iontophoresis appeared non-competitive. The weak, non-specific, and reversible decreased response to inhibitory amino acids observed during moderate to high dose penicillin iontophoresis was interpreted as a secondary phenomenon related to penicillin-induced excitation rather than to receptor antagonism.