Quantitative autoradiographic analysis of the new radioligand [³H](2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6- ylidene) ethanoic acid ([³H]NCS-382) at γ-hydroxybutyric acid (GHB) binding sites in rat brain

(2E)-(5-Hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid (NCS-382) is an antagonist for γ-hydroxybutyric acid (GHB) at GHB receptor sites. Advantages of using [³H]NCS-382 over [³H]GHB in radioligand binding studies are that unlike GHB, NCS-382 does not appear to bind to, activate, or interfere with the functioning of GABA_B or GABA_A receptors, either directly or indirectly. Herein we establish a protocol for use of [³H]NCS-382 by quantitative autoradiography. GHB was used to define non-specific binding, since it displaced [³H]NCS-382 to an extent equivalent to NCS-382. Among many areas of brain examined, two regions in which high specific binding of [³H]NCS-382 occurred were the hippocampus and cerebral cortex. Areas such as the striatum and nucleus accumbens exhibited intermediate levels of specific binding. No or very low binding was observed in other areas such as the cerebellum and dorsal raphe nucleus. The distribution of GHB binding sites as defined by [³H]NCS-382 suggests that GHB may play a role in neuromodulation or neurotransmission in frontal brain areas.