BENZODIAZEPINE(OMEGA) RECEPTOR PARTIAL AGONISTS AND THE ACQUISITION OF CONDITIONED FEAR IN MICE

It is well established that benzodiazepines can produce anterograde am nesia in humans and interfere with the acquisition of passive avoidanc e and spatial responses in rodents. However, the extent to which the d isruption of learning is a secondary effect of the sedation produced b y these drugs has not been clearly established. In order to investigat e this question, the effects of several. BZ (omega) receptor partial a gonists were studied on the acquisition of conditioned fear (passive a voidance learning) in mice. As these drugs have been shown to produce anticonvulsant and anxiolytic-like effects without sedation or depress ion of motor activity, it was of interest to see whether they could di srupt learning. Clear effects on the acquisition of conditioned fear w ere produced by imidazenil (0.01-1.0 mg/kg), divaplon (1-60 mg/kg), ZK 91296 (3-60 mg/kg), and Ro 17-1812 (0.1-10 mg/kg). However, bretazeni l (0.1-10 mg/kg) did not produce statistically significant effects. On ly the high dose of imidazenil (1.0 mg/kg) decreased levels of explora tory behaviour. These results show that BZ (omega) receptor partial ag onists without apparent sedative actions can disrupt fear learning, in dicating that the effects of this class of drugs on passive avoidance learning can be dissociated from sedation. The reasons for the observe d differences between the different compounds studied are unclear at p resent and may be related to differences in intrinsic activity or rece ptor subtype selectivity.