Evaluation of the Serotonergic Genes htr1A, htr1B, htr2A, and slc6A4 in Aggressive Behavior of Golden Retriever Dogs

Berg, Linda van den; Vos-Loohuis, Manon; Schilder, Matthijs B.H.; Oost, B.A. van; Hazewinkel, H. A. W.; Wade, Claire M.; Karlsson, Elinor K.; Lindblad‐Toh, Kerstin; Liinamo, Anna-Elisa; Leegwater, P.A.J.

doi:10.1007/s10519-007-9179-7

Cited by 34 publications

(24 citation statements)

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“…Individuals with the T161 locus had more lifetime aggressive behaviors, and again this polymorphism was linked to reduced transcriptional activity of 5-HT 1B receptors (Sun et al 2002). However, these associations between the HTR1B polymorphisms (G861C, G261T, or C129T) and aggression and antisocial behavior are not seen in other studies (Huang et al 1999; Kranzler et al 2002; New et al 2001; Sinha et al 2003; Van den Berg et al 2008). Based on the findings from pharmacological studies and gene knockout and polymorphism studies, it is likely that the 5-HT 1B receptor has an important role in the inhibition of certain types of aggression.…”

Section: 5-ht Receptorscontrasting

confidence: 59%

“…It is possible that polymorphisms that affect the level of expression of 5-HT 2A receptors can be associated with self-directed aggression. In some samples, a significant linkage was found between polymorphisms in the 5-HT 2A receptor (HTR2A) gene, T102C, A1438G and His452Tyr, and aggressive-impulsive trait or adolescent-onset antisocial behavior in humans (Assal et al 2004; Bjork et al 2002; Burt and Mikolaiewski 2008; Nomura et al 2006), but others have reported no such link between aggression and HTR2A polymorphisms (Khait et al 2005; Van den Berg et al 2008). Again, the successful pharmacotherapeutic management of aggressive patients using compounds with affinity for 5-HT 2A receptors would suggest that violence-prone individuals may be characterized by distinctive HTR2A polymorphisms.…”

Section: 5-ht Receptorsmentioning

confidence: 99%

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Behavioral and Pharmacogenetics of Aggressive Behavior

Takahashi

Quadros

Almeida

et al. 2011

Current Topics in Behavioral Neurosciences

102

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Serotonin (5-HT) has long been considered as a key transmitter in the neurocircuitry controlling aggression. Impaired regulation of each subtype of 5-HT receptor, 5-HT transporter, synthetic and metabolic enzymes has been linked particularly to impulsive aggression. The current summary focuses mostly on recent findings from pharmacological and genetic studies. The pharmacological treatments and genetic manipulations or polymorphisms of a specific target (e.g., 5-HT1A receptor) can often result in inconsistent results on aggression, due to “phasic” effects of pharmacological agents vs “trait”-like effects of genetic manipulations. Also, the local administration of a drug using the intracranial microinjection technique has shown that activation of specific subtypes of 5-HT receptors (5-HT1A and 5-HT1B) in mesocorticolimbic areas can reduce species-typical and other aggressive behaviors, but the same receptors in the medial prefrontal cortex or septal area promote escalated forms of aggression. Thus, there are receptor populations in specific brain regions that preferentially modulate specific types of aggression. Genetic studies have shown important gene × environment interactions; it is likely that the polymorphisms in the genes of 5-HT transporters (e.g., MAO A) or rate-limiting synthetic and metabolic enzymes of 5-HT determine the vulnerability to adverse environmental factors that escalate aggression. We also discuss the interaction between the 5-HT system and other systems. Modulation of 5-HT neurons in the dorsal raphe nucleus by GABA, glutamate, and CRF profoundly regulate aggressive behaviors. Also, interactions of the 5-HT system with other neuropeptides (arginine vasopressin, oxytocin, neuropeptide Y, opioid) have emerged as important neurobiological determinants of aggression. Studies of aggression in genetically modified mice identified several molecules that affect the 5-HT system directly (e.g., Tph2, 5-HT1B, 5-HT transporter, Pet1, MAOA) or indirectly (e.g. BDNF, nNOS, αCaMKII, Neuropeptide Y). The future agenda delineates specific receptor subpopulations for GABA, glutamate and neuropeptides as they modulate the canonical aminergic neurotransmitters in brainstem, limbic and cortical regions with the ultimate outcome of attenuating or escalating aggressive behavior.

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Section: 5-ht Receptorscontrasting

confidence: 59%

Section: 5-ht Receptorsmentioning

confidence: 99%

Behavioral and Pharmacogenetics of Aggressive Behavior

Takahashi

Quadros

Almeida

et al. 2011

Current Topics in Behavioral Neurosciences

102

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“…Reisner et al (128) reported decreased concentrations of a major metabolite of seratonin in cerebrospinal fluid of dominant aggressive dogs, and Badino et al (8) found modifications of serotonergic receptor concentrations in the brains of aggressive dogs. In response, Van den Berg et al (152) evaluated four serotonergic genes with respect to aggressive behavior in golden retrievers. Using mutation screens, linkage analysis, association studies, and quantitative genetic analysis, no obvious associations were found.…”

Section: Canine Behaviormentioning

confidence: 99%

Man's Best Friend Becomes Biology's Best in Show: Genome Analyses in the Domestic Dog

2010

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In the last five years, canine genetics has gone from map construction to complex disease deconstruction. The availability of a draft canine genome sequence, dense marker chips, and an understanding of the genome architecture has changed the types of studies canine geneticists can undertake. There is now a clear recognition that the dog system offers the opportunity to understand the genetics of both simple and complex traits, including those associated with morphology, disease susceptibility, and behavior. In this review, we summarize recent findings regarding canine domestication and review new information on the organization of the canine genome. We discuss studies aimed at finding genes controlling morphological phenotypes and provide examples of the way such paradigms may be applied to studies of behavior. We also discuss the many ways in which the dog has illuminated our understanding of human disease and conclude with a discussion on where the field is likely headed in the next five years.

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“…Serpell and Hsu [26] found the factors consistent for dogs of various breeds and either sex in regard to behavioral traits in guide dogs. Furthermore, Hsu and Serpell developed a questionnaire (Canine behavioral assessment and research questionnaire: C-BARQ) for measuring behavioral traits in pet dogs by using data of 2,054 dogs in the United States [11], and this has been used as the behavioral index in gene studies about behavioral traits of dogs [15,31]. C-BARQ, which evaluates a dog's behavior objectively, can be a powerful tool for screening dogs for behavior problems and in evaluating the clinical effects of various treatments for behaviors [10,29,32].…”

mentioning

confidence: 99%

Assessment of the Factorial Structures of the C-BARQ in Japan

Nagasawa

Tsujimura

Tateishi

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. In order to introduce the Canine Behavioral Assessment and Research Questionnaire (C-BARQ), which is a standardized system for evaluating the behavioral traits of dogs, to Japan, where the environment with respect to dog ownership is thought to differ from those of the United States and Europe, we compared demographic information on dogs in the United States and Japan and examined whether similar factors could be extracted from both countries using questionnaire items of the C-BARQ. The C-BARQ was completed by 11,410, and 734 dog owners respectively in the United States and Japan, and some demographic differences were found, such as breed and neuter status. Data from completed questionnaires were subjected to factor analysis, and the resulting factors were tested for reliability. In the United States, factor analysis yielded 11 factors from 63 items that accounted for 52.9% of the common variance. In Japan, 15 factors were extracted, and these accounted for 57.0% of the common variance. The present factors for the United States were almost identical to the factors identified in a previous study, and similar factors were extracted in both countries. Therefore, the C-BARQ can function effectively as a fundamental behavioral evaluation system for dogs in Japan.KEY WORDS: behavior, canine, C-BARQ, factor analysis, questionnaire.J. Vet. Med. Sci. 73 (7): [869][870][871][872][873][874][875] 2011 In the United States and Europe, behavior problems of dogs account for 17-20% of reasons that owners relinquish their pet dogs to animal shelters, and substantial numbers of these dogs are eventually euthanized [2,5,19,23,25]. In addition, many dogs suffer unnecessarily from inappropriate punishments and aversive training methods as a consequence of behavior problems [8]. These inappropriate treatments for dogs often worsen the problems and create a vicious cycle. In Japan, there were an estimated 13,101,000 pet dogs in 2008 [13]. Of these, 105,195 adult dogs and 24,742 puppies were relinquished to animal shelters [20]. Additional estimates suggest that 29,942 of these dogs were either returned to their owners or adopted by new owners, while 98,556 dogs were eventually euthanized. Because official research has not been conducted yet, it is not known exactly why these dogs were relinquished [20]. In order to resolve these issues, it is important to establish a system for classifying and naming behavioral traits in dogs. Researchers in the United States and Europe have developed some behavioral tests to evaluate the behavioral traits of dogs [14,21,28,30]; however, it is not easy to conduct these behavioral tests, and the possibility exits that the emergence of particular behaviors may be dependent on experimental circumstances during the test. On the other hand, observer ratings can be convenient and useful tools through careful experimental designs [18]. However, observation by third parties has the practical difficulty of observing pet dogs in their natural and home environment. Therefore, in order to understand ...

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Evaluation of the Serotonergic Genes htr1A, htr1B, htr2A, and slc6A4 in Aggressive Behavior of Golden Retriever Dogs

Cited by 34 publications

References 50 publications

Behavioral and Pharmacogenetics of Aggressive Behavior

Behavioral and Pharmacogenetics of Aggressive Behavior

Man's Best Friend Becomes Biology's Best in Show: Genome Analyses in the Domestic Dog

Assessment of the Factorial Structures of the C-BARQ in Japan

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