Low and high doses of benzodiazepine receptor inverse agonists respectively improve and impair performance in passive avoidance but do not affect habituation.

The benzodiazepine receptor inverse agonists, methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) and N-methyl-beta-carboline-3-carboxamide (FG 7142), were given to rats at various stages of a passive avoidance task. When the drugs were given before trial 1, low doses enhanced, and high doses impaired, performance as assessed 24 h later. A group given drugs on both trials showed that the impairment was not due to state-dependent effects.

Selective agonists and antagonists for 5-hydroxytryptamine receptor subtypes, and interactions with yohimbine and FG 7142 using the elevated plus-maze test in the rat.

The effects of some 5-HT receptor ligands were investigated on measures of anxiety in an elevated plus-maze test in the rat. Quipazine (2 and 4 mg kg-1), a non-specific 5-HT agonist and ritanserin (0.25-10 mg kg-1), a 5-HT2 receptor antagonist displayed anxiogenic profiles by reducing both of the measures of anxiety used in this test.

Lack of cross-tolerance in mice between the stimulatory and depressant actions of novel anxiolytics in the holeboard.

CL 218,872, tracazolate and tofisopam are compounds that are believed to act at the GABA-benzodiazepine (BDZ) receptor complex in the CNS and that have anxiolytic properties in animals or in man. Doses of each drug were selected to elevate, or to depress, exploratory head-dipping and locomotor activity in the holeboard in mice, and the development of tolerance to these effects was investigated. As previously found with benzodiazepines, tolerance did not develop to the stimulant effects of low doses of these compounds after 10 days pretreatment with either a low (stimulant) or a high (depressant) dose of the same compound.