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Publication : Benzodiazepine (omega) receptor partial agonists and the acquisition of conditioned fear in mice.

First Author  Sanger DJ Year  1995
Journal  Psychopharmacology (Berl) Volume  121
Issue  1 Pages  104-8
PubMed ID  8539334 Mgi Jnum  J:34698
Mgi Id  MGI:82152 Doi  10.1007/BF02245596
Citation  Sanger DJ, et al. (1995) Benzodiazepine (omega) receptor partial agonists and the acquisition of conditioned fear in mice. Psychopharmacology (Berl) 121(1):104-8
abstractText  It is well established that benzodiazepines can produce anterograde amnesia in humans and interfere with the acquisition of passive avoidance and spatial responses in rodents. However, the extent to which the disruption of learning is a secondary effect of the sedation produced by these drugs has not been clearly established. In order to investigate this question, the effects of several BZ (omega) receptor partial agonists were studied on the acquisition of conditioned fear (passive avoidance learning) in mice. As these drugs have been shown to produce anticonvulsant and anxiolytic-like effects without sedation or depression of motor activity, it was of interest to see whether they could disrupt learning. Clear effects on the acquisition of conditioned fear were 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, bretazenil (0.1-10 mg/kg) did not produce statistically significant effects. Only the high dose of imidazenil (1.0 mg/kg) decreased levels of exploratory behaviour. These results show that BZ (omega) receptor partial agonists without apparent sedative actions can disrupt fear learning, indicating that the effects of this class of drugs on passive avoidance learning can be dissociated from sedation. The reasons for the observed differences between the different compounds studied are unclear at present and may be related to differences in intrinsic activity or receptor subtype selectivity.
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