Possible involvement of GABA(A) and GABA(B) receptors in the inhibitory action of lindane on transmitter release from cerebellar granule neurons

Cerebellar granule cells in culture express receptors for GABA belonging to the GABA(A) and GABA(B) classes. In order to characterize the ability of t he insecticide lindane to interact with these receptors cells were grown in either plain culture media or media containing 150 mu M THIP as this is kn own to influence the properties of both GABA(A) and GABA(B) receptors. It w as found that lin dane regardless of the culture condition inhibited evoked (40 mM K+) release of neurotransmitter ([H-3]D-aspartate as label for glut amate). In naive cells both GABA(A) and GABA(B) receptor active drugs preve nted the inhibitory action of lindane but in THIP treated cultures none of the GABA(A) and GABA(B) receptor active drugs had any effect on the inhibit ory action of lindane. This lack of effect was not due to inability of bacl ofen itself to inhibit transmitter release. It is concluded that lindane de pendent on the state of the GABA(A) and GABA(B) receptors is able to indire ctly interfere with both GABA(A) and GABA(B) receptors. In case of the latt er receptors it was shown using [H-3]baclofen to label the receptors that l indane could not displace the ligand confirming that lindane is likely to e xert its action at a site different from the agonist binding site.