Bidirectional effects on anxiety of ß-carbolines acting as benzodiazepine receptor ligands

Abstract Although the antipunishment activity of anxiolytic benzodiazepine (BZ) receptor ligands correlated with their binding potency in vivo, certain s-carboline ligands enhanced the punishing effects of footshock and antagonised diazepam's antipunishment action. Similar bidirectional effects were seen in rats trained to discriminate between pentylenetetrazol (PTZ) and saline injections to obtain food in an operant task. BZ-like s-carbolines antagonised the PTZ cue whereas those with propunishment properties substituted for it. The direction of the effect of s-carbolines depended on whether they enhanced (anxiolytic) or inhibited binding of 35S-TBPS to the GABA/BZ-receptor/chloride ionophore (GBC) complex.