RO 15-4513 does not protect rats against the lethal effects of ethanol.

In two separate research centres the ability of RO 15-4513 to protect rats against the lethal effects of ethanol (7.5 and 15 g/kg) was investigated. In neither study did RO 15-4513 offer protection against ethanol-induced lethality or the loss of righting reflex caused by these doses of ethanol.

Interactions of the imidazodiazepine Ro 15-4513 with chemical convulsants.

1. The proconvulsant effects of the imidazodiazepine Ro 15-4513, were investigated in mice by use of intravenous infusion of a variety of convulsant drugs. 2.

Behavioral interactions of fluoxetine and other 5-hydroxytryptamine uptake inhibitors with ethanol in tests of anxiety, locomotion and exploration.

The 5HT uptake inhibitor fluoxetine had no effect on motor activity or directed exploration (head-dipping) in a holeboard test or in an elevated plusmaze test of anxiety. Fluoxetine (20 mg/kg) attenuated the anxiolytic effect of a 2.4 g/kg dose of ethanol in the plusmaze but failed to alter ethanol's effects on exploratory head-dipping or locomotion.

The effects of novelty, isolation, light and ethanol on the social behavior of mice.

The social behavior of pairs of male NIH Swiss mice was assessed under a variety of experimental conditions. Increasing periods of isolation increased both the total time spent in social interaction and also increased the incidence of aggressive behavior. Familiarity with the testing arena tended to increase social behavior, but the magnitude of this effect was considerably less than that previously observed in rats.

Interactions of 5HT reuptake inhibitors and ethanol in tests of exploration and anxiety.

Treatment with 5HT reuptake inhibitors has been shown to attenuate ethanol consumption in both animals and humans. These experiments investigate in mice the interactions of the 5HT reuptake inhibitors fluoxetine, citalopram and fluvoxamine and the NA uptake inhibitor desipramine with ethanol in the holeboard test and the elevated plusmaze test of anxiety. Ethanol (2.

Time course of ethanol's effects on locomotor activity, exploration and anxiety in mice.

The time course of the effects of two doses of ethanol on exploration, locomotor activity and anxiety were investigated using the holeboard and plus-maze tests. In an 8 min holeboard test the lower (1.2 g/kg) dose increased both exploration and locomotor activity 0.

Clinical relevance of effects of benzodiazepines on learning and memory.

The effects of benzodiazepines on learning and memory are examined in the various clinical situations in which these drugs are used. Alterations in performance arising from the conditions for which benzodiazepines are prescribed are also considered. Current evidence indicates that, in anxious patients, as in normal volunteers, benzodiazepines impair the acquisition of new information (episodic memory).

RO 15-4513 and its interaction with ethanol.

It has recently been claimed that RO 15-4513 selectively opposes some of the behavioral actions of ethanol. Our studies on the intrinsic effects of this compound have shown it to be proconvulsant and to reduce exploratory behavior in mice. In these respects RO 15-4513 resembles a benzodiazepine receptor partial inverse agonist.

Behavioral interactions between ethanol and imidazodiazepines with high affinities for benzodiazepine receptors.

The intrinsic effects of two imidazodiazepines RO 15-3505 and RO 17-1812 on the behavior of mice in a holeboard test were investigated. The interactions of these two drugs with ethanol were also studied. RO 15-3505 (0.

The benzodiazepine receptor inverse agonists FG 7142 and RO 15-4513 both reverse some of the behavioral effects of ethanol in a holeboard test.

The intrinsic effect of the benzodiazepine receptor inverse agonists RO 15-4513 and FG 7142 on the behavior of mice in a holeboard were investigated. Both drugs caused dose-related decreases in exploratory head-dipping. The highest dose of FG 7142 (40 mg/kg) also reduced locomotor activity.

Mapping of a putative genetic locus determining ethanol intake in the mouse.

In the mouse, there is evidence that a single genetic locus is a major determinant of differences in ethanol intake between some preferring and non-preferring inbred strains. In this report, we present evidence from two independent experiments indicating that this locus maps to chromosome 1 and that its expressed product is the abundant protein LTW-4 (a 28 kDa, pI 5.6 protein expressed in brain, liver and kidney).

RO 15-4513 induces seizures in DBA/2 mice undergoing alcohol withdrawal.

RO 15-4513, an imidazodiazepine that has been reported to reverse some of the behavioral effects of ethanol, was given to DBA/2 mice. Although no animals treated with a 6 mg/kg dose of this drug had seizures, 20% of animals given 20 mg/kg of this drug had tonic seizures. Ethanol withdrawal was induced in DBA/2 mice treated with 4-methyl pyrazole using an inhalation paradigm.

Interactions of Ro 15-4513 with diazepam, sodium pentobarbital and ethanol in a holeboard test.

Ro 15-4513 (1.5 mg/kg) decreased the exploratory activity of mice in a holeboard test. This effect was reversed by diazepam (1 mg/kg), ethanol (1 g/kg) and sodium pentobarbital (15 mg/kg).

Reversal of the intrinsic effects of Ro 15-4513 on exploratory behavior by two benzodiazepine receptor antagonists.

In a holeboard test the imidazodiazepine Ro 15-4513 (1.5 and 3.0 mg/kg) reduced exploratory head-dipping.

The effect of the imidazodiazepine Ro 15-4513 on the anticonvulsant effects of diazepam, sodium pentobarbital and ethanol.

The ability of the imidazodiazepine Ro 15-4513 to antagonize the anticonvulsant effects of diazepam, sodium pentobarbital and ethanol was investigated. Ro 15-4513 alone significantly lowered seizure threshold to bicuculline and this effect subtracted from the anticonvulsant effects of sodium pentobarbital and ethanol. In contrast, Ro 15-4513 completely reversed the anticonvulsant effects of diazepam, consistent with suggestions that it is a competitive ligand for benzodiazepine receptors.

The effect of chlordiazepoxide on the habituation of exploration: interactions with the benzodiazepine antagonist RO 15-1788.

Rats tested on two occasions in a holeboard apparatus showed between-session habituation of exploratory activity. No habituation was observed on the measure of locomotor activity. Administration of chlordiazepoxide before the first test reduced exploratory behavior in this test and also reduced the degree of between-session habituation.

The effects of ethanol on exploration in DBA/2 and C57Bl/6 mice.

The effect of ethanol (0.8, 1.6, and 2.

Ethanol intoxication and memory. Recent developments and new directions.

A qualitative description of the acute effects of ethanol intoxication on learning and memory is presented. Mechanisms underlying the acquisition impairments observed in intoxicated subjects are discussed. Recent studies on retroactive facilitation are also considered.

Neuropharmacological strategies for understanding psychobiological determinants of cognition.

Psychopharmacological methods that have proven useful in exploring brain processes can be helpful in describing the psychobiological determinants of distinct cognitive processes. The methods and theory in current cognitive science can be exploited by neuropharmacologists interested not only in describing brain function but in building a viable picture of brain-behavior (cognitive) relationships. This paper provides a sketch of our knowledge about the neuropharmacology of cognitive processes.

The use of a plus-maze to measure anxiety in the mouse.

To investigate whether an elevated plus-maze consisting of two open and two closed arms could be used as a model of anxiety in the mouse, NIH Swiss mice were tested in the apparatus immediately after a holeboard test. Factor analysis of data from undrugged animals tested in the holeboard and plus-maze yielded three orthogonal factors interpreted as assessing anxiety, directed exploration and locomotion. Anxiolytic drugs (chlordiazepoxide, sodium pentobarbital and ethanol) increased the proportion of time spent on the open arms, and anxiogenic drugs (FG 7142, caffeine and picrotoxin) reduced this measure.

The effects of repeated doses of ethanol on exploration and its habituation.

The effects of ethanol (0.8-2.4 g/kg) on exploratory behavior and its habituation were investigated by testing DBA/2 mice in a holeboard apparatus.

Mice and rats are sensitized to the proconvulsant action of a benzodiazepine-receptor inverse agonist (FG 7142) following a single dose of lorazepam.

Rats and mice were treated with lorazepam (1.0 mg/kg) or its vehicle. Six h later seizure threshold to i.