Comparison of Behavioral Effects of GABAergic Low- and High-Efficacy Neuroactive Steroids in the Zebrafish Larvae Assay.

ABSTRACT: Activation of the GABA_A receptor is associated with numerous behavioral end points ranging from anxiolysis to deep anesthesia. The specific behavioral effect of a GABAergic compound is considered to correlate with the degree of its functional effect on the receptor. Here, we tested the hypothesis that a low-efficacy allosteric potentiator of the GABA_A receptor may act, due to a ceiling effect, as a sedative with reduced and limited action. We synthesized a derivative, named (3α,5β)-20-methyl-pregnane-3,20-diol (KK-235), of the GABAergic neurosteroid 5β-pregnane-3α,20α-diol. Using electrophysiology, we showed that KK-235 is a low-efficacy potentiator of the synaptic-type α1β2γ2L GABA_A receptor. In the zebrafish larvae behavioral assay, KK-235 was found to on

SUBMITTER: Germann AL 

PROVIDER: S-EPMC10953468 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature