Attenuation of defensive threat and attack in wild rats (Rattus rattus) by benzodiazepines

Dc, Blanchard; Hori, Kevin; Rodgers, R.J.; Ca, Hendrie; Rj, Blanchard

doi:10.1007/bf00439457

Cited by 70 publications

(22 citation statements)

References 46 publications

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“…Except for a decrease in the duration of walking and an increase in crouch behaviors, diazepam was without effect on orienting, upright, rearing, and escape activity. These findings are concordant with the observations that nondefensive measures of locomotor behavior in rats (i.e., rearing, grooming) were inconsistently altered by diazepam (Rodgers and Randall 1987;Blanchard et al 1989Blanchard et al , 1990a. Depending on the intensity of the "anxiety"-producing stimulus, increases and decreases were observed on defensive measures including crouch postures (Blanchard et al 1990b).…”

Section: Discussionsupporting

confidence: 87%

Diazepam and gepirone selectively attenuate either 20–32 or 32–64 kHz ultrasonic vocalizations during aggressive encounters

Vivian

Miczek

1993

Psychopharmacology

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Ultrasonic vocalizations (USV) in rats may communicate "affective" states, as they occur only in highly significant behavioral contexts such as during sex, aggression, exposure to painful or startling events. This proposal was evaluated in an experiment with adult male Long-Evans rats during agonistic encounters; specifically, the effects of diazepam, flumazenil and gepirone were studied on different types of USV emitted by intruder rats exposed to resident attacks and to "threat of attacks" (i.e., intruder protected within the home cage of the resident by a wire mesh cage). USV were readily emitted during agonistic encounters and consisted primarily of two distributions of pure tone whistles: 0.3- to 3-s, 20- to 32-kHz ("low") signals and 0.02- to 0.3-s, 32- to 64-kHz ("high") signals. A considerable repertoire of frequency modulated signals was observed and proved to be sensitive to the anxiolytic treatments. Diazepam (1-6 mg/kg) dose-dependently decreased high frequency USV during the threat of attack and decreased the mean pitch of the most predominant vocalizations but did not affect low frequency USV or the audible squeals (AS) in response to bites. Gepirone (0.3-6 mg/kg) dose-dependently decreased low frequency USV and did not affect high frequency USV or AS. Responses to thermal pain stimuli remained unaltered by all drugs, while walking duration was decreased and crouch postures were increased after diazepam but not after gepirone administration. Gepirone in the present dose range had minimal effects on submissive, exploratory and locomotor behaviors. The pattern of results is consistent with the proposal that low frequency USV reflect a heightened affective state which is ameliorated with 5HT1A but not benzodiazepine anxiolytics, and suggests that the suppression of high frequency USV in reaction to attacks or threats coincides with the sedative or muscle relaxant properties of these compounds.

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Section: Discussionsupporting

confidence: 87%

Diazepam and gepirone selectively attenuate either 20–32 or 32–64 kHz ultrasonic vocalizations during aggressive encounters

Vivian

Miczek

1993

Psychopharmacology

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“…Thus, pharmacological studies using this task (Blanchard et al, 1988(Blanchard et al, , 1989a(Blanchard et al, ,b, 1991bRodgers et al, 1990;Shepherd et al, 1993) routinely employed wildtrapped R. norvegicus and Rattus rattus. The task was labeled the Fear/Defense Test Battery to reflect that it involved those defensive behaviors (e.g.…”

Section: The Fear/defense Test Batterymentioning

confidence: 99%

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

Blanchard

Griebel

Blanchard

2003

European Journal of Pharmacology

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258

159

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The Mouse Defense Test Battery was developed from tests of defensive behaviors in rats, reflecting earlier studies of both acute and chronic responses of laboratory and wild rodents to threatening stimuli and situations. It measures flight, freezing, defensive threat and attack, and risk assessment in response to an unconditioned predator stimulus, as well as pretest activity and postthreat (conditioned) defensiveness to the test context. Factor analyses of these indicate four factors relating to cognitive and emotional aspects of defense, flight, and defensiveness to the test context. In the Mouse Defense Test Battery, GABA A -benzodiazepine anxiolytics produce consistent reductions in defensive threat/attack and risk assessment, while panicolytic and panicogenic drugs selectively reduce and enhance, respectively, flight. Effects of GABA A -benzodiazepine, serotonin, and neuropeptide ligands in the Mouse Defense Test Battery are reviewed. This review suggests that the Mouse Defense Test Battery is a sensitive and appropriate tool for preclinical evaluation of drugs potentially effective against defense-related disorders such as anxiety and panic. D

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“…For example, benzodiazepines (BDZ) have been consistently found to reduce aggressive behavior in a large number of species (for review: see Rodgers 1991;Miczek et al 1995). However, at lower doses especially, these compounds have been also been reported to produce "paradoxical" increases in aggression (Miczek 1974;Krsiak 1975;Miczek and O'Donnell 1980;Rodgers and Waters 1985;Yoshimura and Ogawa 1989;Olivier et al 1991;Palanza et al 1996), effects that may be related to basal levels of aggression and /or anxiety Blanchard et al 1989;Rodgers 1991). Interestingly, other drugs which act at the GABAA receptor complex (such as ethanol) also produce biphasic effects on aggressive behavior in various species (for review, see Miczek et al 1994a).…”

Section: Introductionmentioning

confidence: 97%

Differential effects of chlordiazepoxide on aggressive behavior in male mice: the influence of social factors

et al. 1997

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The present study examined the influence of prior social experience on the effects of chlordiazepoxide (CDP; 5.0, 10.0 and 20.0 mg/kg) on intrasexual aggression in male mice. Prior to drug testing, animals were either individually housed or screened in dyadic encounters in a neutral cage. This novel method yielded four experimental groups comprising animals with different social experiences and different aggressive/defensive characteristics: 1) individually-housed males (I): 2) aggressive males (A); 3) counter-attacking males (C), which actively responded to but did not initiate attack; and 4) defeated males (D). Twenty-four hours after screening, animals were treated with CDP and subjected to a resident-intruder test with untreated intruders. Results indicated that the lowest dose of CDP (5 mg/kg) increased aggressive behaviour but only in A males. At higher doses (10-20 mg/kg), CDP reduced attacks towards intruders in A, C and I, but not D, males. In A and C males, the antiaggressive action of CDP was associated with a prosocial effect (increased social investigation), whereas in I males, reduced aggression was associated with an increase in fear-related behaviours. As these differential effects of CDP on intermale aggression cannot be fully explained by differences in behavioural baselines, present data highlight the importance of experiential background as a powerful variable in determining behavioural responses to benzodiazepines. Present findings therefore suggest that an understanding of drug effects on social behaviour demands consideration of biological variability in phenotype.

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Attenuation of defensive threat and attack in wild rats (Rattus rattus) by benzodiazepines

Cited by 70 publications

References 46 publications

Diazepam and gepirone selectively attenuate either 20–32 or 32–64 kHz ultrasonic vocalizations during aggressive encounters

Diazepam and gepirone selectively attenuate either 20–32 or 32–64 kHz ultrasonic vocalizations during aggressive encounters

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

Differential effects of chlordiazepoxide on aggressive behavior in male mice: the influence of social factors

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