Quantitative and comparative analyses of pro-aggressive actions of benzodiazepines in maternal aggression of rats

Olivier, Berend

doi:10.1007/bf00442238

Cited by 35 publications

(21 citation statements)

References 5 publications

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“…One striking detail was that for each dam injected with CDP (8/8), aggression was increased relative to baseline. Our findings are consistent with previous studies showing that lower doses of CDP, as well with other BDZs, such as diazepam and oxazepam, facilitate maternal aggression (Ferreira et al, 2000;Grimes et al, 2006;Mos and Olivier, 1989;Yoshimura and Ogawa, 1991). Although CDP could be elevating normal levels of maternal aggression, an alternative hypothesis is that experimental treatment (e.g., isoflurane, handling, injection) induce some impairment of maternal aggression and that CDP is mitigating that effect.…”

Section: Discussionsupporting

confidence: 92%

“…Dose was based on previous literature (D 'Amato et al, 1997;Mos and Olivier, 1989;Olivier et al, 1985;Palanza et al, 1996;Yoshimura and Ogawa, 1989). All injections were interperitoneal (i.p).…”

Section: Pharmacological Treatment and Injectionmentioning

confidence: 99%

“…Previous studies showed that BDZ agonists (which increase the binding affinity of GABA onto GABA A receptors) alter maternal aggression in rats (Ferreira et al, 2000;Mos and Olivier, 1989;Olivier et al, 1985) and mice (Palanza et al, 1996;Ogawa, 1989, 1991) with low doses increasing and higher doses inhibiting aggression. Where and how BDZs act centrally to modify maternal defense, though, is not known.…”

Section: Introductionmentioning

confidence: 99%

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GABA enhancement of maternal defense in mice: Possible neural correlates

Lee

Gammie

2007

Pharmacology Biochemistry and Behavior

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Previous studies have shown that low doses of GABA A receptor agonists facilitate maternal defense of offspring (maternal aggression), without significantly affecting other maternal behaviors. In addition, it has been demonstrated that endogenous changes in GABAergic neurotransmission occur in association with lactation. This study investigated the effects of GABA A receptor agonist, chlordiazepoxide (CDP), a benzodiazepine (BDZ), on maternal behaviors including aggression, and identified brain regions with altered activity in association with treatment. Another aim of the study was to determine whether CDP injections could prevent decreases in maternal aggression that occur with pup separation. Intraperitoneal injections of 1mg/kg of CDP significantly increased maternal defense without affecting other maternal behaviors, although a trend towards elevated nursing was noted. CDP significantly reduced c-Fos in lateral septum (LS) and caudal periaqueductal gray (cPAG) in behaviorally-experienced mice relative to vehicle-injected controls. In behaviorally-naïve subjects, CDP also decreased c-Fos in LS, but in cPAG this decrease was just above significance (p = 0.051). CDP was not sufficient to "rescue" maternal aggression when pup stimulus was removed. Overall, these studies provide further insights into the role for GABA in maternal behaviors, including aggression, and how and where BDZs may act to modulate behavior.

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Section: Discussionsupporting

confidence: 92%

Section: Pharmacological Treatment and Injectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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GABA enhancement of maternal defense in mice: Possible neural correlates

Lee

Gammie

2007

Pharmacology Biochemistry and Behavior

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“…File 1980), diazepam has recently been reported to be ineffective as an anxiolytic in socially-defeated intruder rats (Tornatzky and Miczek 1995). It is well known that, like alcohol and barbiturates, BDZ show a biphasic effect on aggressive behavior with stimulation at low doses and inhibition at high doses (Miczek 1974;Miczek and Krsiak 1979;Mos and Olivier 1989;Miczek et al 1995). Some authors have suggested that BDZ-induced enhancement of aggression may occur more easily when animals are naive, are confronted with a more difficult situation, or have a low baseline level of aggression (Mos and Olivier 1988;.…”

Section: Discussionmentioning

confidence: 99%

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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“…The trazodone induced a biphasic behavior with the lowest dose causing a proaggressive effect that was transformed into antiaggressive responses at higher doses ( Figure 1). It is interesting to note that Rush et al (1997) stated that the pharmacological profile of trazodone is qualitatively similar to the benzodiazepine hypnotics, several of which also produce a biphasic response for aggression with an increase of offensive behavior at low and decrease at higher doses (Mos and Olivier, 1989;Yoshimura and Ogawa, 1989).…”

Section: Trazodone: 5-ht Antagonistmentioning

confidence: 96%

5-Hydroxytryptamine (Serotonin): Biphasic Dose Responses

Calabrese

2001

Critical Reviews in Toxicology

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This article briefly summarizes the occurrence of biphasic dose-response relationships associated with 5-hydroxytryptamine (5-HT) receptor systems, as well as 5-HT agonists and antagonists. Such biphasic responses have been reliably reported in multiple experimental settings that explored a broad range of responses, including aggressive behavior, cardiovascular functioning, muscle relaxation, and interactions with other receptor systems such as adrenergic interaction as well as with neurotransmitters such as NMDA.

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Quantitative and comparative analyses of pro-aggressive actions of benzodiazepines in maternal aggression of rats

Cited by 35 publications

References 5 publications

GABA enhancement of maternal defense in mice: Possible neural correlates

GABA enhancement of maternal defense in mice: Possible neural correlates

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

5-Hydroxytryptamine (Serotonin): Biphasic Dose Responses

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