The effect of α2 adrenoceptor blockers on aggressive behavior in mice: implications for the actions of adrenoceptor agents

Haller, József; Makara, Gábor B.; Kovács, József

doi:10.1007/bf02247386

Cited by 17 publications

(8 citation statements)

References 39 publications

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“…Immobility in the forcedswim procedure is reduced by ␣ 2 -AR antagonists and genetic deletion of ␣ 2C -ARs (Sallinen et al, 2007;Millan, 2010). ␣ 2 -ARs antagonists also reduce aggressive behavior (Haller et al, 1996;M. Brocco, unpublished observation), suppress marble burying (Lä hdesmä ki et al, 2002), and block S18616-induced LRR .…”

Section: Tablementioning

confidence: 91%

S32212, a Novel Serotonin Type 2C Receptor Inverse Agonist/α2-Adrenoceptor Antagonist and Potential Antidepressant: II. A Behavioral, Neurochemical, and Electrophysiological Characterization

Dekeyne¹,

Brocco²,

Loiseau³

et al. 2012

The Journal of Pharmacology and Experimental Therapeutics

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The present studies characterized the functional profile of N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-1,2-dihydro-3-H-benzo-[e]indole-3-carboxamide) (S32212), a combined serotonin (5-HT) 2C receptor inverse agonist and ␣ 2 -adrenoceptor antagonist that also possesses 5-HT 2A antagonist properties (J Pharmacol Exp Ther 340: [750][751][752][753][754][755][756][757][758][759][760][761][762][763][764] 2012). Upon parenteral and/or oral administration, dosedependent (0.63-40.0 mg/kg) actions were observed in diverse procedures. Both acute and subchronic administration of S32212 reduced immobility time in a forced-swim test in rats. Acutely, it also suppressed marble burying and aggressive behavior in mice. Longterm administration of S32212 was associated with rapid (1 week) and sustained (5 weeks) normalization of sucrose intake in rats exposed to chronic mild stress and with elevated levels of mRNA encoding brain-derived neurotrophic factor in hippocampus and amygdala (2 weeks). S32212 accelerated the firing rate of adrenergic perikarya in the locus coeruleus and elevated dialysis levels of noradrenaline in the frontal cortex and hippocampus of freely moving rats. S32212 also elevated the frontocortical levels of dopamine and acetylcholine, whereas 5-HT, amino acids, and histamine were unaffected. These neurochemical actions were paralleled by "promnemonic" properties: blockade of scopolamine-induced deficits in radial maze performance and social recognition and reversal of delay-induced impairments in social recognition, social novelty discrimination, and novel object recognition. It also showed anxiolytic actions in a Vogel conflict procedure. Furthermore, in an electroencephalographic study of sleep architecture, S32212 enhanced slowwave and rapid eye movement sleep, while decreasing waking. Finally, chronic administration of S32212 neither elevated body weight nor perturbed sexual behavior in male rats. In conclusion, S32212 displays a functional profile consistent with improved mood and cognitive performance, together with satisfactory tolerance.

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Section: Tablementioning

confidence: 91%

S32212, a Novel Serotonin Type 2C Receptor Inverse Agonist/α2-Adrenoceptor Antagonist and Potential Antidepressant: II. A Behavioral, Neurochemical, and Electrophysiological Characterization

Dekeyne¹,

Brocco²,

Loiseau³

et al. 2012

The Journal of Pharmacology and Experimental Therapeutics

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“…Some behavioural variance may have been introduced by the fact that resident mice encountered NMRI mice, whereas mice of the same genotype were paired in the social interaction test. However, earlier experience with these strains shows that their aggressiveness is rather similar, but largely sensitive to environmental stressors (Haller et al ., 1996). Therefore, it is highly probable that environmental differences (home vs. unfamiliar cage) had a considerably larger effect on behaviour than the potential small differences in the opponent's behaviour.…”

Section: Methodsmentioning

confidence: 99%

Context‐dependent effects of CB1 cannabinoid gene disruption on anxiety‐like and social behaviour in mice

Haller

Varga

Ledent

et al. 2004

Eur J of Neuroscience

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261

203

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Contrasting data were reported regarding the effects of cannabinoids on anxiety and social behaviour in both animals and humans. The cognitive effects of cannabinoids and their interactions with the HPA-axis raise the possibility that cannabinoid effects are context but not behaviour specific. To assess this hypothesis, we submitted CB1 receptor knock-out (CB1-KO) and wild-type (WT) mice to tests, which involved similar behaviours, but the behavioural context was different. The elevated plus-maze test was performed under less and more anxiogenic conditions, i.e. under low and high light, respectively. We also compared the social behaviour of the two genotypes in the resident/intruder and social interaction tests. Both tests represent a social challenge and induce similar behaviours, but involve different contexts. The behaviour of CB1-KO and WT mice was similar under low light, but CB1 gene disruption increased anxiety-like behaviour under the high light condition. CB1 gene disruption promoted aggressive behaviour in the home-cage, whereas it inhibited social behaviour in the unfamiliar cage. Thus, the anxiogenic-like effect was restricted to the more stressful unfamiliar environment. These data suggest that the effects of CB1 gene disruption were context and not behaviour specific. Novelty stress resulted in higher ACTH levels in CB1-KOs than in WTs, which suggests that context dependency occurred in conjunction with an altered HPA axis function. The present data at least partly explain contrasting effects of cannabinoids in different contexts as well as in different species and strains that show differential stress responses and coping strategies.

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“…The effect of a 2 -AR antagonists (e.g. yohimbine, idazoxan) is mostly anxiogenic [Blanchard et al, 1993] and antiaggresive [Haller et al, 1996;Kemble et al, 1991], but they also enhanced aggression in several studies [Ferrari and Giuliani, 1993;Gentsch et al, 1989;Haller et al, 1994].…”

Section: Introductionmentioning

confidence: 99%

Selective antiaggressive effect of an alpha‐2 adrenoceptor agonist naphthylmedetomidine in mice

Votava

Hess

Kršiak

2008

Aggressive Behavior

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Alpha-2 adrenoceptors (alpha(2)-ARs) are critically involved in regulating neurotransmitter release from sympathetic nerves and neurons and play an important role in the regulation of awareness, arousal and vigilance. In our recent study, dexmedetomidine, a full alpha(2)-AR agonist, produced antiaggressive effects in the social conflict test in mice at doses that were twice smaller than those producing sedation. The aim of this study was to ascertain antiaggressive effect of a novel drug naphthylmedetomidine, with a more selective alpha(2)-AR activity. Behavioral effects of naphthylmedetomidine (150-1200 microg/kg i.p.) were studied in the activity cage and in the social conflict tests in mice. Naphthylmedetomidine dose dependently decreased aggressive behavior during social conflict in aggressive mice with significant reduction already at the lowest doses tested (150 microg/kg), whereas locomotion and social investigation were significantly decreased only after four times bigger dose of naphthylmedetomidine (600 microg/kg) in aggressive mice. Naphthylmedetomidine had no effect on aggression in nonaggressive mice. Naphthylmedetomidine reduced locomotion in the activity cage significantly only at the highest doses tested (600 and 1200 microg/kg), and this effect was only partially reversed by administration of high doses of an alpha-2 antagonist atipamezole (3 and 10 mg/kg). In nonaggressive mice, the difference between the dose reducing dominant social behavior (social investigation) and locomotion (150 and 300 microg/kg, respectively) was smaller than in aggressive mice. In conclusion, naphthylmedetomidine showed a very strong and selective antiaggressive effect in aggressive mice, which was devoid of locomotion-inhibiting/sedative effect. This study suggests that naphthylmedetomidine may have clinical potential as antiaggressive drug.

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The effect of α2 adrenoceptor blockers on aggressive behavior in mice: implications for the actions of adrenoceptor agents

Cited by 17 publications

References 39 publications

S32212, a Novel Serotonin Type 2C Receptor Inverse Agonist/α2-Adrenoceptor Antagonist and Potential Antidepressant: II. A Behavioral, Neurochemical, and Electrophysiological Characterization

S32212, a Novel Serotonin Type 2C Receptor Inverse Agonist/α2-Adrenoceptor Antagonist and Potential Antidepressant: II. A Behavioral, Neurochemical, and Electrophysiological Characterization

Context‐dependent effects of CB1 cannabinoid gene disruption on anxiety‐like and social behaviour in mice

Selective antiaggressive effect of an alpha‐2 adrenoceptor agonist naphthylmedetomidine in mice

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