Absence of 5-HT1B receptors is associated with impaired impulse control in male 5-HT1B knockout mice

Bouwknecht, J. Adriaan; Hijzen, Theo H.; Gugten, Jan van der; Maes, R. A. A.; Hen, René; Olivier, Berend

doi:10.1016/s0006-3223(00)01018-0

Cited by 137 publications

(98 citation statements)

References 56 publications

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“…Specifically, 5-HT 1B knockout mice appear to be more aggressive toward intruders than their conspecific wild-type mice (Bouwknecht et al, 2001;Ramboz et al, 1996;Saudou et al, 1994). These findings are supported by the established antiaggressive properties of a class of 5-HT 1B receptor agonists (such as eltoprazine), termed serenics, in animals (de Almeida Olivier, Mos, Van Oorschot, & Hen, 1995).…”

Section: The 5-ht 1b Receptor and Serotonergic Genesmentioning

confidence: 84%

The evidence for a neurobiological model of childhood antisocial behavior.

Goozen¹,

Fairchild²,

Snoek³

et al. 2007

Psychological Bulletin

414

393

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Children with persistent antisocial and aggressive behavior are diagnosed as having disruptive behavior disorder. The authors review evidence that antisocial children, and especially those who persist with this behavior as they grow older, have a range of neurobiological characteristics. It is argued that serotonergic functioning and stress-regulating mechanisms are important in explaining individual differences in antisocial behavior. Moreover, low fear of punishment and physiological underactivity may predispose antisocial individuals to seek out stimulation or take risks and may help to explain poor conditioning and socialization. The authors propose a theoretical model highlighting the interplay between neurobiological deficits and cognitive and emotional functioning as mediators of the link between early adversity and antisocial behavior problems in childhood. Implications for intervention programs are discussed.

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Section: The 5-ht 1b Receptor and Serotonergic Genesmentioning

confidence: 84%

The evidence for a neurobiological model of childhood antisocial behavior.

Goozen¹,

Fairchild²,

Snoek³

et al. 2007

Psychological Bulletin

414

393

View full text Add to dashboard Cite

show abstract

“…It was particularly noteworthy in individuals that show high levels of aggression as a result of social instigation or alcohol treatment (Fish et al .1999;de Almeida et al 2001;Rilke et al 2001). In addition, anpirtoline inhibits anxiety-like and depression-like behaviors, pain, and sexual behavior (Schlicker et al 1992;Metzenauer et al 1992;Hillegaart and Ahlenius 1998;Bouwknecht et al 2001;O'Neill and Conway 2001). The reduction in aggression was antagonized by GR127935, indicated by a rightward shift in the doseeffect curves of anpirtoline, demonstrating the 5-HT 1B receptors as the key site of action.…”

Section: Discussionmentioning

confidence: 96%

Aggression Escalated by Social Instigation or by Discontinuation of Reinforcement (“Frustration”) in Mice Inhibition by Anpirtoline: A 5-HT1B Receptor Agonist

Almeida

2002

Neuropsychopharmacology

140

104

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Experiments with social instigation or the omission of scheduled reinforcement show that serotonergic mechanisms may be involved in escalated aggression in animals. 5-HT 1B receptor agonists have anti-aggressive effects in individuals who show moderate as well as high levels of aggression. The present study compared the effects of the 5-HT 1B agonist anpirtoline (0.125-1.5 mg/kg) on (1) species-typical aggressive behavior in male mice, (2) aggression "instigated" or primed by prior exposure to the opponent, and (3) aggression heightened by "frustration" caused by omission of scheduled reinforcement. The effects of anpirtoline on species-typical behavior were also assessed after pretreatment with the 5-HT 1B/1D receptor antagonist GR127935 (10 mg/kg). Anpirtoline, like other 5-HT 1Bagonists 253, zolmitriptan) The development of valid experimental protocols that model clinically relevant, excessive levels of aggressive behavior is a continuing challenge for pre-clinical research on aggression (Miczek 2001). The leading neurobiological hypothesis attributes such intense aggressive behavior, often related to expressions of impulsivity, to a deficit in brain serotonin (Linnoila et al. 1983;Virkkunen et al. 1989;Coccaro 1989). An early example of this research strategy was the demonstration that mice would exhibit intense aggressive behavior after prolonged isolated housing, and this isolation-induced aggression is associated with lower serotonin turnover in the brainstem ). Long-standing concerns with the validity and reliability of isolation-induced aggression and its limited species generality prompt the search for alternate approaches (Brain 1975;Krsiak 1975). Similarly, correlation of aggressive behavior with a single tissue or CSF measurement of serotonin or its metabolite need to be reconciled with the anti-aggressive effects of agonist NO . 2 and antagonist treatment of specific serotonin receptor subtypes (Olivier et al. 1995;de Almeida et al. 2001).The exposure of an experimental subject to a potential rival for a short time prior to the actual confrontation engenders intense levels of aggression, as originally described in mice (Lagerspetz 1969;Tellegen and Horn 1972). For example, mice, rats, and hamsters initiate attacks with very short latency and at high frequency when tested with an intruder in their home cage or in an unfamiliar locale after having been provoked previously by an opponent (Potegal 1992;Fish et al. 1999). Instigation or priming is specific for increasing aggressive behavior and does not activate locomotion, feeding, or sexual behavior (Lagerspetz and Hautojarvi 1967;Potegal and Tenbrink 1984;Potegal 1992). Even after removal of the instigating or priming stimulus, high levels of aggression persist in fish and rodents, presumably from increased "aggressive arousal" or "attack readiness" (Heiligenberg 1974;Potegal and Tenbrink 1984;Potegal 1992). At the neurochemical level, animals that have been instigated to fight are characterized by a long-lasting decrease in serotonin in hypoth...

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“…Once administered, serotonin agonists, which include 5-hydroxytryptophan, L-tryptophan and selective serotonin reuptake inhibitors, markedly attenuate hyperactivity in the DAT-KO mice. 34 In addition, mice lacking the 5HT1B receptor show hyperactivity, increased aggression and behavioral deinhibition [35][36][37][38][39] and 5HT4 receptor knockout mice show attenuated novelty-induced exploratory activity. 40 Finally, 5HT2 receptor agonists modulate hyperlocomotor activity in rats, and monoamine oxidase inhibitors reduce impulsiveness in animal models of ADHD.…”

Section: Introductionmentioning

confidence: 99%

Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB

et al. 2007

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Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in which different genetic and environmental susceptibility factors are involved. Several lines of evidence support the view that at least 30% of ADHD patients diagnosed in childhood continue to suffer the disorder during adulthood and that genetic risk factors may play an essential role in the persistence of the disorder throughout lifespan. Genetic, biochemical and pharmacological studies support the idea that the serotonin system participates in the etiology of ADHD. Based on these data, we aimed to analyze single nucleotide polymorphisms across 19 genes involved in the serotoninergic neurotransmission in a clinical sample of 451 ADHD patients (188 adults and 263 children) and 400 controls using a population-based association study. Several significant associations were found after correcting for multiple testing: (1) the DDC gene was strongly associated with both adulthood (P = 0.00053; odds ratio (OR) = 2.17) and childhood ADHD (P = 0.0017; OR = 1.90); (2) the MAOB gene was found specifically associated in the adult ADHD sample (P = 0.0029; OR = 1.90) and (3) the 5HT2A gene showed evidence of association only with the combined ADHD subtype both in adults (P = 0.0036; OR = 1.63) and children (P = 0.0084; OR = 1.49). Our data support the contribution of the serotoninergic system in the genetic predisposition to ADHD, identifying common childhood and adulthood ADHD susceptibility factors, associations that are specific to ADHD subtypes and one variant potentially involved in the continuity of the disorder throughout lifespan.

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Absence of 5-HT1B receptors is associated with impaired impulse control in male 5-HT1B knockout mice

Cited by 137 publications

References 56 publications

The evidence for a neurobiological model of childhood antisocial behavior.

The evidence for a neurobiological model of childhood antisocial behavior.

Aggression Escalated by Social Instigation or by Discontinuation of Reinforcement (“Frustration”) in Mice Inhibition by Anpirtoline: A 5-HT1B Receptor Agonist

Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB

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