ACUTE HANDLING STRESS DOWN-REGULATES BENZODIAZEPINE RECEPTORS - REVERSAL BY DIAZEPAM

In rats naive to handling, the effects of an acute handling stress led to lower [H-3]flunitrazepam binding in the frontal cortex, compared with animals previously habituated to handling for 2 or 21 days. This decreased binding was due to reductions in the number of receptors, not to a change in affinity. Pre-incubation with diazepam (0.3, 3.0 or 30-mu-M) of frontal cortex homogenates taken from naive rats exposed to acute handling stress (followed by extensive washing to remove residual diazepam and endogenous modulators) led to a concentration-dependent increase in the number of benzodiazepine receptors, without any change in K(D). Acute in vivo administration of diazepam (4 mg/kg) prior to the handling stress was without significant effect in handling-habituated animals, but increased [H-3]flunitrazepam binding in handling naive rats. Thus, handling habituation and diazepam treatment have similar actions on benzodiazepine binding and represent two ways of adapting to the stress of handling by increasing the number of benzodiazepine receptors.