Corticotropin releasing factor and amphetamine exaggerate partial agonist properties of benzodiazepine antagonist Ro 15-1788 in the conflict test

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Abstract
The central nervous system stimulants corticotropin releasing factor (CRF) and amphetamine were administered in combination with the benzodiazepine ligands Ro 15-1788 and FG 7142 in order to assess their benzodiazepine agonist and antagonist receptor properties in an operant conflict test in rats. Ro 15-1788, which was without behavioral activity in this test when given alone, reversed the suppression of punished responding produced by CRF and amphetamine in a dose-dependent manner. Chlordiazepoxide, which produced a release of punished responding by itself, also reversed the suppression of punished responding produced by CRF but not that of amphetamine. The benzodiazepine inverse agonist FG 7142, in contrast, enhanced the rate suppressing actions of both CRF and amphetamine. In a locomotor activity test, Ro 15-1788 failed to block the locomotor activation observed with CRF and amphetamine. The results suggest that “anxiety” or stress-enhancing compounds may enhance the partial agonist properties of Ro 15-1788 in certain test situations.