Differential effects of anxiolytic and non-anxiolytic benzodiazepine receptor ligands on performance of a differential reinforcement of low rate (DRL) schedule.
The effects of several drugs acting at central benzodiazepine receptors on performance of a differential reinforcement of low rate (DRL) 15s schedule of reinforcement for food reward were studied in rats. The non-selective full agonists diazepam (0.1, 1.25, 5 and 10mg/kg) and lorazepam (0.1, 0.25, 0.375 and 0.5mg/kg) increased total numbers of responses and decreased the numbers of reinforcements received, increased burst responding (responding within 3s of a previous response), and produced a shift in the interresponse time (IRT) distribution of responses towards shorter intervals. The beta-carboline anxiolytic abecarnil (0.039, 0.156, 0.313 and 0.625mg/kg) was more potent than the two benzodiazepines, but otherwise gave rise to similar changes in performance. Bretazenil (0.1, 1.0, 10 and 30mg/kg), a non-selective partial agonist, and CL 218872 (3, 10, and 30mg/kg), a partial agonist showing preference for the BZ1 receptor subtype, also increased response rates and decreased numbers of reinforcements, but failed to increase significantly burst responding, and had only weak effects in shifting the IRT distribution. Alpidem (1, 3, 10, 30 and 100mg/kg) and zolpidem (0.33, 1, 3 and 10mg/kg), two imidazopyridines showing BZ1 preference, but classified respectively as an anxiolytic and a selective hypnotic agent, non-significantly reduced response rates and significantly reduced the numbers of reinforcements, but did not influence burst responding, and had effects on IRT distribution only at single doses. Thus, in general, the effects of these compounds on DRL performance reflect their activity in conflict models. The differential effects on DRL performance of the benzodiazepine receptor ligands tested may be attributable to their abilities to interact selectively as agonists or partial agonists at different benzodiazepine receptor subtypes.
Stephens
D.N.
DN
Department of Neuropsychopharmacology, Research Laboratories of Schering AG, D-13342 Berlin, Germany.
Voet
B.
B