A NEUROPHARMACOLOGICAL STUDY OF GAMMA-AMINOBUTYRYLCHOLINE, GAMMA-AMINOBUTYRIC ACID, PHYSOSTIGMINE AND ATROPINE

¹ Departments of Anatomy and Pharmacology, University of California School of Medicine, Los Angeles, California

In the unanesthetized, immobilized cat, neocortical responses evoked by stimulation of a variety of brain sites were studied for possible sensitivity to gamma - aminobutyrylcholine (GABCh), gamma-aminobutyric acid (GABA), physostigmine, atropine and atropine methylnitrate. In addition, the effects of intraventricular administrations of GABCh, GABA and physostigmine were compared in terms of alterations in affective behavior, in neurological symptoms and in seizure patterns elicited by thiosemicarbazide. The actions of GABCh were found to be different from those of GABA and physostigmine in the following ways: (1) intravenous administration (1 to 10 mg/kg) and topical application to the neocortex (0.1 to 5%) of GABCh failed to alter a variety of neocortical evoked potentials; (2) GABCh failed to interact with the effects of GABA on the same responses; (3) intraventricular administration of GABCh produced hyperexcitability, motor incoordination, a curious skulking behavior and enhancement of the convulsive effects of thiosemicarbazide. GABA produced depression without motor incoordination and mollified thiosemicarbazide seizures. Physostigmine Produced hyperexcitability, nondirected aggression without loss of motor coordination and had no demonstrable effects on the convulsive pattern produced by thiosemicarbazide.

Atropine methylnitrate (0.5 to 5 mg/kg i.v.) caused no consistent changes in the EEG and minimal changes in the cortical evoked responses.

Physostigmine at doses of 50 to 100 mg/kg intravenously produced the characteristic EEG pattern of low voltage, fast activity and reductions in the amplitude of the negative components of the evoked recruiting and sensory responses recorded from the anterior sigmoid gyrus. At the same time, the superficially evoked surface negative response in this area was little affected. In contrast, the superficial response recorded from the medial suprasylvian gyrus was clearly attenuated.

Atropine sulfate counteracted the effects of physostigmine on both the cortical evoked potentials and on the EEG patterns. Atropine in the unpremedicated animals caused the appearance of the characteristic high voltage, slow waves in the EEG and had minimal effects on cortical-evoked potentials. Atropine enhanced the effects of GABA on the cortical responses but did not affect the activity of GABCh.