LINDANE BLOCKS GABA(A)-MEDIATED INHIBITION AND MODULATES PYRAMIDAL CELL EXCITABILITY IN THE RAT HIPPOCAMPAL SLICE

An in vitro paired-pulse orthodromic stimulation technique was used to examine the effects of lindane on excitatory afferent terminals, CA1 pyramidal cells and recurrent collateral evoked inhibition in the rat hippocampal slice. This was done to establish simultaneous effects on a simple neural network and to develop procedures for more detailed an alyses of the effects of lindane. Hippocampal slices 400 mu m thick we re perfused with oxygenated artificial cerebrospinal fluid. Electrodes were placed in the CA1 region to record extracellular population spik e (PS) or excitatory postsynaptic potential (EPSP) responses to stimul ation of Schaffer collateral/commissural (SC/C) fibers. Gamma-aminobut yric acid (GABA)-mediated recurrent inhibition was measured using a pa ired-pulse technique. Perfusion with lindane produced both time and do se dependent changes in a number of the responses measured. The most s triking effect produced by lindane was the loss of GABA(A)-mediated re current collateral inhibition. This tended to occur rapidly, often bef ore changes in EPSP or PS responses could be detected. With longer exp osures to lindane, repetitive discharge of pyramidal cells developed r esulting in multiple PSs to single stimuli. Lindane (50 uM) also compl etely reversed the effects of the injectable anesthetic, propofol, a c ompound known to potentiate GABA(A)-mediated inhibition via a direct a ction on the GABA(A) receptor-chloride channel complex. An analysis of input/output relationships at varying stimulus intensities showed tha t lindane increased EPSP and PS response amplitudes at any given stimu lus intensity resulting in a leftward shift in the EPSP amplitude/stim ulus intensity, PS amplitude/stimulus intensity and PS amplitude/EPSP amplitude relationships. This effect was most noticeable with low inte nsity stimuli and became progressively less so as stimulus intensifies approached those yielding maximal responses. In addition lindane sign ificantly increased paired pulse facilitation of EPSPs during paired s timulus presentation. (C) 1995 Intox Press, Inc.