Neuro-imaging the serotonin 2A receptor as a valid biomarker for canine behavioural disorders

Vermeire, Simon; Audenaert, Kurt; Meester, Rudy De; Vandermeulen, Eva; Waelbers, Tim; Spiegeleer, Bart De; Eersels, Jos; Dobbeleir, André; Peremans, Kathelijne

doi:10.1016/j.rvsc.2010.09.021

Cited by 26 publications

(14 citation statements)

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“…Violent impulsive humans have lower levels of 5-HIAA in cerebrospinal fluid than violent individuals who had committed a crime with premeditation (Virkkunen et al, 1995). In dogs, impulsive individuals have lower levels of 5-HIAA in cerebrospinal fluid than nonimpulsive ones (Reisner et al, 1996;Quadros et al, 2010), and there is a lower activity of serotonin receptors in some areas of brain in impulsive dogs compared with nonimpulsive ones (Peremans et al, 2003;Vermeire et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Differences in serotonin serum concentration between aggressive English cocker spaniels and aggressive dogs of other breeds

Amat

Brech

Camps

et al. 2013

Journal of Veterinary Behavior

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Section: Discussionmentioning

confidence: 99%

Differences in serotonin serum concentration between aggressive English cocker spaniels and aggressive dogs of other breeds

Amat

Brech

Camps

et al. 2013

Journal of Veterinary Behavior

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“…In future studies, lower doses should be used in cats as well. Increased BIs (baseline scans) are seen in dogs with behavioral disorders (37). The cats used in this study showed no obvious behavioral disorders, but investigation for behavioral disorders by specialists was beyond the scope of the study.…”

Section: Discussionmentioning

confidence: 77%

5-HT_2AReceptors in the Feline Brain:¹²³I-5-I-R91150 Kinetics and the Influence of Ketamine Measured with Micro-SPECT

et al. 2013

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Subanesthetic doses of ketamine can be used as a rapid-acting antidepressant in patients with treatment-resistant depression. Therefore, the brain kinetics of 123 I-5-I-R91150 (4-amino-N-[1-[3-(4-fluorophenyl)propyl]-4-methylpiperidin-4-yl]-5-iodo-2-methoxybenzamide) and the influence of ketamine on the postsynaptic serotonin-2A receptor (5-hydroxytryptamine-2A, or 5-HT 2A ) status were investigated in cats using micro-SPECT. Methods: This study was conducted on 6 cats using the radioligand 123 I-5-I-R91150, a 5-HT 2A receptor antagonist, as the imaging probe. Anesthesia was induced and maintained with a continuous-rate infusion of propofol (8.4 6 1.2 mg kg 21 followed by 0.22 mg kg 21 min 21 ) 75 min after tracer administration, and acquisition of the first image began 15 min after induction of anesthesia. After this first acquisition, propofol (0.22 mg kg 21 min 21 ) was combined with ketamine (5 mg kg 21 followed by 0.023 mg kg 21 min 21 ), and the second acquisition began 15 min later. Semiquantification, with the cerebellum as a reference region, was performed to calculate the 5-HT 2A receptor binding indices (parameter for available receptor density) in the frontal and temporal cortices. The binding indices were analyzed with Wilcoxon signed ranks statistics. Results: The addition of ketamine to the propofol continuous-rate infusion resulted in decreased binding indices in the right frontal cortex (1.25 6 0.22 vs. 1.45 6 0.16; P 5 0.028), left frontal cortex (1.34 6 0.15 vs. 1.49 6 0.10; P 5 0.028), right temporal cortex (1.30 6 0.17 vs. 1.45 6 0.09; P 5 0.046), and left temporal cortex (1.41 6 0.20 vs. 1.52 6 0.20; P 5 0.046). Conclusion: This study showed that cats can be used as an animal model for studying alterations of the 5-HT 2A receptor status with 123 I-5-I-R91150 micro-SPECT. Furthermore, an interaction between ketamine and the 5-HT 2A receptors resulting in decreased binding of 123 I-5-I-R91150 in the frontal and temporal cortices was demonstrated. Whether the decreased radioligand binding resulted from a direct competition between ketamine and 123 I-5-I-R91150 or from a decreased affinity of the 5-HT 2A receptor caused by ketamine remains to be elucidated.

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“…However, these groups are quite distinct both behaviorally and ecologically [28,69]. Studies on the serotonin system have shown that it is connected with behaviors characteristic of invasive species [5-15,33-35] and it has been argued that genetic variation in serotonin functioning may allow a species to exploit more habitats [31], potentially through increased plasticity [70,71]. Outside of humans, M. mulatta has the widest geographic distribution of all primates and their fossil record indicates a long history of expansion [23].…”

Section: Discussionmentioning

confidence: 99%

“…It has been hypothesized that the exploitation of a large part of the world by both humans and macaques was the result of the evolution of similar behavioral strategies, such as high between-group aggression [31,32]. Such behaviors are often related to serotonin functioning [5,6,12-15] and are hypothesized to comprise a "behavioral syndrome" characteristic of invasive species [33-35]. In line with this theory, several similar, though independently evolved, genetic variants related to serotonin functioning have been identified in both rhesus macaques and humans, most notably SLC6A4 [36] and MAOA [13], and this has been argued to be the result of similar selective pressures acting on the serotonin system [31].…”

Section: Introductionmentioning

confidence: 99%

Patterns of genetic variation and the role of selection in HTR1A and HTR1B in macaques (Macaca)

et al. 2014

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BackgroundResearch has increasingly highlighted the role of serotonin in behavior. However, few researchers have examined serotonin in an evolutionary context, although such research could provide insight into the evolution of important behaviors. The genus Macaca represents a useful model to address this, as this genus shows a wide range of behavioral variation. In addition, many genetic features of the macaque serotonin system are similar to those of humans, and as common models in biomedical research, knowledge of the genetic variation and evolution of serotonin functioning in macaques are particularly relevant for studies of human evolution. Here, we examine the role of selection in the macaque serotonin system by comparing patterns of genetic variation for two genes that code for two types of serotonin receptors – HTR1A and HTR1B – across five species of macaques.ResultsThe pattern of variation is significantly different for HTR1A compared to HTR1B. Specifically, there is an increase in between-species variation compared to within-species variation for HTR1A. Phylogenetic analyses indicate that portions of HTR1A show an elevated level of nonsynonymous substitutions. Together these analyses are indicative of positive selection acting on HTR1A, but not HTR1B. Furthermore, the haplotype network for HTR1A is inconsistent with the species tree, potentially due to both deep coalescence and selection.ConclusionsThe results of this study indicate distinct evolutionary histories for HTR1A and HTR1B, with HTR1A showing evidence of selection and a high level of divergence among species, a factor which may have an impact on biomedical research that uses these species as models. The wide genetic variation of HTR1A may also explain some of the species differences in behavior, although further studies on the phenotypic effect of the sequenced polymorphisms are needed to confirm this.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-014-0116-5) contains supplementary material, which is available to authorized users.

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Neuro-imaging the serotonin 2A receptor as a valid biomarker for canine behavioural disorders

Cited by 26 publications

References 65 publications

Differences in serotonin serum concentration between aggressive English cocker spaniels and aggressive dogs of other breeds

Differences in serotonin serum concentration between aggressive English cocker spaniels and aggressive dogs of other breeds

5-HT_2AReceptors in the Feline Brain:¹²³I-5-I-R91150 Kinetics and the Influence of Ketamine Measured with Micro-SPECT

Patterns of genetic variation and the role of selection in HTR1A and HTR1B in macaques (Macaca)

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Neuro-imaging the serotonin 2A receptor as a valid biomarker for canine behavioural disorders

Cited by 26 publications

References 65 publications

Differences in serotonin serum concentration between aggressive English cocker spaniels and aggressive dogs of other breeds

Differences in serotonin serum concentration between aggressive English cocker spaniels and aggressive dogs of other breeds

5-HT2AReceptors in the Feline Brain:123I-5-I-R91150 Kinetics and the Influence of Ketamine Measured with Micro-SPECT

Patterns of genetic variation and the role of selection in HTR1A and HTR1B in macaques (Macaca)

Contact Info

Product

Resources

About

5-HT_2AReceptors in the Feline Brain:¹²³I-5-I-R91150 Kinetics and the Influence of Ketamine Measured with Micro-SPECT