Strychnine-sensitive glycine receptors inducing [3H]-acetylcholine release in rat caudatoputamen: a new site of action of ethanol?

Abstract

In the present study acute effects of ethanol on [³H]-acetylcholine ([³H]-ACh) release induced by activation of strychnine-sensitive glycine receptors in superfused slices of rat caudatoputamen were investigated. The glycine-evoked [³H]-ACh release (lg EC₅₀ = –4.10, CI₉₅ = [–4.14, –4.05]) was inhibited by strychnine in a competitive manner (pA₂ = 6.86, CI₉₅ = [6.61, 7.08]). Release of [³H]-ACh could also be induced by L-serine. L-serine was less potent than glycine (lg EC₅₀ = –2.61, CI₉₅ = [–2.69, –2.52]). Both glycine and L-serine showed similar maximum effects (E_max(glycine) = 1.34, CI₉₅ = [1.24, 1.45]; E_{max(L-serine)} = 1.19, CI₉₅ = [1.09, 1.32]). Ethanol at concentrations of 2‰ (= 34 mM) and 4‰ (= 68 mM) inhibited glycine-evoked [³H]-ACh release in a manner like the competitive antagonist strychnine, however with lower potency. The pA₂ of ethanol was 1.19, CI₉₅ = [0.85, 1.41], at 2‰ [v/v] and 1.51, CI₉₅ = [1.19, 1.78] at 4‰ ethanol. Similar to its action on glycine-evoked [³H]-ACh release, ethanol at 4‰ [v/v] also inhibited L-serine-evoked transmitter release in a competitive-like fashion (pA₂ = 0.83, CI₉₅ = [–0.15, 1.18]). We conclude, that strychnine-sensitive glycine receptors, mediating [³H]-ACh release in the rat caudatoputamen, might represent a new site of action of ethanol.