Antidepressant treatment and rodent aggressive behaviour

Mitchell, Paul J.

doi:10.1016/j.ejphar.2005.09.029

Cited by 57 publications

(45 citation statements)

References 63 publications

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“…By analogy to marble burying, suppression of aggressive behavior in isolated mice is an empirical screen not easily related to core deficits of depression, despite the high incidence of aggression and irritability in patients (Millan et al, 2001;Millan, 2006;Dekeyne et al, 2008;Malkesman et al, 2009). In view of its reduction by S32212, it would be interesting to determine whether S32212 specifically affects agonistic behavior under other conditions (Mitchell 2005) and whether it affects behavior in models of social defeat (Razzoli et al, 2009;Carr and Lucki, 2011). Reversal by S32212 of the motor-depressant action (LRR) of S18616 mimics numerous antidepressants and has been putatively related to the relief of psychomotor retardation (Millan et al, 2001;Dekeyne et al, 2008).…”

Section: Tablementioning

confidence: 99%

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. 2011

J Pharmacol Exp Ther

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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: 99%

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. 2011

J Pharmacol Exp Ther

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“…Additionally, a number of recent studies, looking at specific local changes, or specific receptor activity, cast doubt on inhibitory regulatory effect of 5-HT on aggression (de Boer and Koolhaas, 2005; de Almeida et al, 2005). Even antidepressant treatments, including selective 5-HT reuptake inhibitors, have been demonstrated to increase aggression in rats when administered chronically (Mitchell, 2005;Mitchell and Redfern, 1997;Mitchell and Redfern, 1992). Recent work on the 5-HT 3 receptor in hamsters demonstrates that action at this receptor can have both stimulatory and inhibitory effects on aggression (Ricci et al, 2005;Ricci et al, 2004).…”

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confidence: 99%

Interactions between the neural regulation of stress and aggression

Summers

Winberg

2006

Journal of Experimental Biology

183

155

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Socially aggressive interaction is stressful. What is more, social aggression is stressful for both dominant and subordinate animals. Much of the neurocircuitry for stress and aggression overlap. The pattern of neurochemical and hormonal events stimulated by social interaction make it clear that subtle differences in this pattern of response distinguish social rank. The neurotransmitter serotonin (5-HT) responds rapidly to stress, and also appears to play the most important role for inhibitory regulation of aggressive interactions. In addition, the adrenocortical/ interrenal steroid hormones corticosterone and cortisol are responsive to stress and influence aggression. However, while 5-HT and glucocorticoids can both be inhibitory to aggression, the relationship between 5-HT and glucocorticoids is not straightforward, and much of the distinctions in function depend upon timing. Neither is inhibitory during the early stressful phase of aggression. This transmitter-hormone combination follows and influences a four-stage functional pattern of effect: (1) predisposed (positively or negatively) toward aggression, (2) motivated toward behavior, (3) responsive to stress (including aggression) and passively allowing aggression, and finally (4) chronically applied 5-HT and glucocorticoids inhibit aggression.Key words: antagonism, attack, corticosterone, cortisol, dominant, dopamine (DA), fight, hostility, serotonin (5-HT), social stress, stages, subordinate, timeline. territorial animals that must constantly protect resources, most of the time aggressive tendencies are held in check. Revealing aggressive potential is the consequence of numerous provocations in the normal life history of most animals and humans. Therefore, in this review, we will consider neural systems that stimulate aggression, but we will focus on inhibitory regulation. That inhibitory regulation emanates primarily from one neurotransmitter system, serotonin (5-HT) (Nelson and Chiavegatto, 2001), but it is far from simple. Its complex nature is derived from neuroendocrine relationships between stress and aggression. The timeline on which these two interacting systems are co-expressed take place before, during and after socially aggressive interaction (Fig.·1). The timeline is suggested as a model of aggressive interaction in all vertebrates, but we especially draw from examples of evolutionarily conserved behavior and neuroendocrine adaptation in fish and lizards (Winberg and Nilsson, 1993;Summers et al., 2005c). We describe neurotransmitter and hormonal responses during four stages, where they: (1) influence predisposition (positively or negatively) toward aggression, (2) motivate behavior (3) are responsive to stress (including aggression) but passively allow aggression and finally (4) may chronically inhibit aggression. Summary Aggression neurocircuitryExperimental inhibitory effects of 5-HT on aggressive behavior are most often the result of systemic application of serotonergic drugs, like selective 5-HT reuptake inhibitors (SSRI; usually a stage 4...

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“…The situation in man is more complex than for instance in the cat [20] or the rat [21] on account of mankind's far greater linguistic skill. In man all sensory information can be replaced by language symbols and aggression can be expressed entirely in a linguistic way.…”

Section: Ssris and Violencementioning

confidence: 99%

“…Of these two forms of aggression there is an example in rodents where administering anti-depressants had the opposite effect, namely, the inhibition of defensive aggression and the promotion of assertive aggression [21]. It is postulated that in order to initiate these two forms, there is in principle an emotional, affective or "hot" form of aggression as well as a cognitive, instrumental or "cold" one.…”

Section: Ssris and Violencementioning

confidence: 99%

Aspects of Causality: A Verdict Inquiry of a Case with SSRI Use

Brouwers¹,

Loonen²,

Nielen³

et al. 2014

JHS

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Sometimes more than one expert advises the court. They use different notional frameworks in doing so, and may report different opinions about the case they examined. In this case, the authors discuss the relation between the use of a SSRI (serotonin reuptake inhibitor) and a fatal tragedy in a family where the mother was accused of killing her husband and daughter a few days after use of the SSRI. No fewer than seven experts were heard (four behavioral experts, one behavioral toxicologist, one pharmacist and one pharmacologist) at the ensuing trial, and various possible diagnoses were dealt with in the experts' reports and at trial. More attention must be paid to the mentally debilitating influence of SSRI medication on certain psychological functions shortly after its intake. Although a mono-causal relationship between that influence and the accused's intention is necessary to exculpate the accused from guilt, the authors believe that a singular connection is never happened in the case.

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Antidepressant treatment and rodent aggressive behaviour

Cited by 57 publications

References 63 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

Interactions between the neural regulation of stress and aggression

Aspects of Causality: A Verdict Inquiry of a Case with SSRI Use

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Antidepressant treatment and rodent aggressive behaviour

Cited by 57 publications

References 63 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

Interactions between the neural regulation of stress and aggression

Aspects of Causality: A Verdict Inquiry of a Case with SSRI Use

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Product

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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