Effects of Original Compounds GSB-106, GML-3, and GZK-111 in an Experimental Lipopolysaccharide-Induced Anhedonia Model

Abstract

Antidepressant activities of the original compounds GSB-106 [bis(N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide], a mimetic of the fourth loop of brain-derived neurotrophic factor (BDNF); GML-3(N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide), a ligand of 18 kDa translocator protein (TSPO); and GZK-111 (N-phenylacetylglycyl-L-proline ethyl ester), a substitute dipeptide that is biotransformed into the neuropeptide cyclo-L-prolylglycine that affects AMPA receptors; were previously revealed at V. V. Zakusov Institute of Pharmacology in experimental models of the depressive state caused by unescapable stress conditions. The present article studied the antidepressant effects of GSB-106, GML-3, and GZK-111 in an inflammatory model of the depressive state induced by lipopolysaccharide (LPS) in male C57Bl/6 mice with an assessment of anhedonia based on the consumption of sucrose solution. LPS in a single dose of 0.5 mg/kg intraperitoneally (i.p.) caused a marked decrease of 39% (p ≤ 0.01) in the consumption of 1% sucrose solution as compared to the control group. GSB-106 administered perorally at a dose of 0.5 mg/kg 24 h after LPS increased by 20% (p ≤ 0.05) sucrose consumption reduced by LPS in mice. GML-3 administered once perorally at doses of 0.5 and 1.0 mg/kg increased sucrose consumption by 29 and 21% (p ≤ 0.01), respectively. GZK-111 administered once i.p. at a dose of 1.0 mg/kg increased sucrose consumption by 17% (p ≤ 0.05). The obtained data confirmed the antidepressant properties of GSB-106, GML-3, and GZK-111.