Variation in behavioral response to baclofen: correlation with benzodiazepine binding sites in mouse forebrain

Mice treated with (+/-)baclofen (2 mg/kg i.p.) displayed profound differences to the motor depressant action of this drug. Mice were divided into three groups termed as responders (20%), moderate responders (65%) and nonresponders (15%). No differences were detected in the spontaneous motor activity between the selected groups. When the animal population in the home cages was kept unchanged the different responses to baclofen were reproducible three weeks after selection. A borderline dose of diazepam (1.5 mg/kg) decreased highly significantly motor activity in baclofen responders but failed to do this in nonresponders group. Ex vivo studies with 3H-flunitrazepam (labelling in vivo and binding carried out in vitro) demonstrated that 3H-flunitrazepam binding in mouse forebrain was significantly smaller in baclofen responders than in nonresponders. Further, the apparent number of 3H-flunitrazepam binding sites in vitro was significantly decreased in the forebrain of baclofen responders. It is concluded that some actions of baclofen depend on the functional state of benzodiazepine recognition sites.