Chronic treatment of mice with the specific gamma-aminobutyrie acid(B) (GABA(B)) receptor antagonist (2S)(+)-5.5-(dimethyl-2-morpholineacetic acid (SCH 50,911) increased both the number of GABA(B) receptors in the whole brain (measured as [H-1]CGP 54626 [S-(R,R)]-3-[[1-(3,4-dichlorophenyl)amino]-2-hydroxypropyl](cyclohexylmethyl)phosphinic acid hydrochloride binding) and the ability of bacloten to activate GABA(B) receptor coupled G-protein (measured as % reduction of the EC50 of baclofen to activate [S-15]GTP gamma S binding). The results indicate that persistent blockade of GABA(B) receptors leads to their compensatory up-regulation and suggest that GABA(B) receptors are tonically activated by endogenous GABA. (c) 2005 Elsevier B.V. All rights reserved.