Diazepam, Pentobarbital, And Methaqualone Effects On Several Behaviors In The Rat And Antagonism By Ro 15-1788

The sedative hypnotics may exert their effects through a number of different mechanisms. Diazepam interacts with a specific receptor linked to a GABA receptor and a CL ionophore (Skolnick and Paul, 1981) and enhances the binding affinity of the GABA receptor for its ligand. Barbiturates may act at an additional receptor linked to this complex (Olsen, 1981). The sites of action of methaqualone have yet to be defined. Recently Hunkeler et al. (1981) synthesized a new class of compounds, the imidazodiazepines, the prototype being Ro 15-1788. They showed that Ro 15-1788 inhibits 3H-Diazepam binding to brain synaptosomes, reverses diazepam-induced protection against metrazol seizures, and alleviates the disruption induced by diazepam in a horizontal wire test. Ro 15-1788 does not affect the depression induced by Phenobarbital, meprobamate or ethanol. In a standard conflict paradigm Ro 15-1788 prevents the antipunishment effect of diazepam. Ro 15-1788 also antagonizes the decrease in rat cerebellar cGMP by diazepam, but not that by barbiturates, ethanol or meprobamate (Mohler et al., 1981), and reverses the effects of 3-methylclonazepam in a number of tests in humans (Darragh et al., 1981). We have investigated the effects of diazepam (DZ), pentobarbital (PB) and methaqualone (MQ) alone and in combination with Ro 15-1788 in a novel conflict paradigm, conditioned suppression of drinking (CSD), as well as in rotarod performance (RR) and motor activity (MA)