Modulation of noradrenaline release from hippocampal slices by hexachlorocyclohexane isomers. Effects of GABAergic compounds

Abstract

The effects of hexachlorocyclohexane (HCH) isomers and some GABAergic compounds on [ 3H]noradrenaline (NA) release from rat hippocampal slices prelabelled with 80 nM [ 3H]NA were determined. The convulsant γ-HCH isomer facilitated (EC 50 = 21 μM) and the depressant δ-HCH isomer reduced (EC 50 = 48 μM) the Ca 2+-dependent K +-evoked release of [ 3H]NA, whereas α- and β-HCH isomers did not show any effect. Moreover, α- and δ-HCH isomers antagonized the facilitation of evoked [ 3H]NA release induced by the γ-HCH isomer. The GABAergic convulsant drugs, bicuculline, picrotoxin and pentylenetetrazol, did not cause any modification of the evoked [ 3H]NA release even at high concentrations. Neither bicuculline nor picrotoxin blocked the effects of HCH isomers on K +-evoked release of [ 3H]NA. Exposure of slices to diazepam reduced the K +-evoked release of [ 3H]NA (EC 50 = 33 μM) in a manner similar to that of the δ-HCH isomer. In addition, diazepam (50 μM) blocked the γ-HCH effect and caused an additive inhibitory response with the δ-HCH isomer. On the other hand, diazepam and δ-HCH induced a time-dependent Ca 2+-independent enhancement of basal [ 3H]NA release. The results suggest that modulation of [ 3H]NA release in the hippocampus by HCH isomers may be involved in the central actions of these compounds, and that sites other than the classic GABA A receptor may underlie their presynaptic mechanisms of action.