Neuronal responses to putative neurotransmitters during penicillin epileptogenesis.
An epileptogenic process was induced within the rat frontoparietal cortex by microiontophoretic applications of penicillin. The temporal development of the penicillin-induced activity was divided into (a) a first phase characterized by an increased rate of neuronal firing, (b) a pre-paroxysmal phase wherein neurons began to fire clusters of action potentials and (c) a paroxysmal phase characterized by a discharge of action potential clusters. The excitatory responses to glutamate and to acetylcholine appeared to be enhanced during the first and pre-paroxysmal phases, whereas a loss of the excitatory effectiveness of both glutamate and acetylcholine occurred during the final paroxysmal phase. Forty nine of 69 neurons studied (71%) showed a decreased sensitivity to gamma-aminobutyrate during the first phase of penicillin iontophoresis. However, during this same time, glycine-induced inhibition was not decreased. During the second phase, gamma-aminobutyrate-induced inhibition was even less effective, and glycine started to lose effectiveness. During the third phase, both these inhibitory neurotransmitters failed to affect the neuronal activity. The other 29% of the neurons studied showed a general diminution to the actions of both gamma-aminobutyrate and glycine when penicillin-induced action potential clusters appeared. Our results suggest that penicillin interferes with gamma-aminobutyrate-mediated inhibition in a large proportion of cortical neurons of the rat. Furthermore, these cortical neurons show changes in the responses to both excitatory and inhibitory neurotransmitters that closely parallel the development of penicillin-induced activity.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology; D004827:Epilepsy / Q000139:chemically induced*; D007478:Iontophoresis; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D010406:Penicillins / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D018377:Neurotransmitter Agents; D010406:Penicillins