Rat pup isolation distress and the brain benzodiazepine receptor

Pharmacologic studies have demonstrated that benzodiazepines can modulate the ultrasonic vocalizations (USV) associated with social separation of rat pups. In this study, in vivo receptor autoradiography was used to determine if brain benzodiazepine receptors were functionally less available to bind an exogenous ligand during social separation. The labeled benzodiazepine receptor antagonist. 3H-RO 15-1788, was given to 10-day-old rat pups with varying schedules of social separation. In initial studies with homogenized and solubilized tissue, we found a 30% reduction in binding to cortex when pups were separated for 25 min beginning 5 min prior to tracer injection. In subsequent autoradiographic studies with this same separation schedule, the binding of 3H-RO 15-1788 was examined in 21 brain regions. Again binding was decreased in neocortex (frontal, motor, and somatosensory). In addition, we found significantly decreased binding in hippocampus, dentate gyrus, and superior and inferior colliculi. These same regions showed no alteration of in vitro binding of 3H-RO 15-1788. Therefore, these decreases in in vivo binding do not reflect changes in receptor number. The interpretation of decreased in vivo binding and implications of these results for defining the neural substrates of separation behavior are discussed.