Behavioral effects of systemically administered MK-212 are prevented by ritanserin microinfusion into the basolateral amygdala of rats exposed to the elevated plus-maze

Cruz, Antônio Pedro de Mello; Pinheiro, Gilson de Assis; Alves, Sandra Mara Campos; Ferreira, Graziela; Mendes, M. C.; Faria, Letícia Rodrigues; Macedo, Carlos Eduardo; Landeira-Fernández, J.

doi:10.1007/s00213-005-0108-2

Cited by 70 publications

(33 citation statements)

References 83 publications

(119 reference statements)

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“…For example, hypoactivity in the elevated plus maze can overcome the detection of anxiogenic-like effects in some experimental manipulations [60] but not in others [61]. Moreover, a motor effect in the elevated plus maze can be part of the defense response to an anxiogenic compound [62].…”

Section: Problem Of Locomotor Activitymentioning

confidence: 99%

Behavioral evaluation of eight rat lines selected for high and low anxiety-related responses

Gomes

Hassan

Maisonnette

et al. 2013

Behavioural Brain Research

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evaluation of eight rat lines selected for high and low anxiety-related responses" (2013 • Genetic models are powerful tools to help understand anxiety disorders.• In order to determine the extent to which multiple anxiety traits generalize we compared eight genetic lines of rats selected for single high or low emotional responses.• We find many behavioral traits generalize across different animal lines selected for a single trait. a b s t r a c t Anxiety traits can be stable and permanent characteristics of an individual across time that is less susceptible of influences by a particular situation. One way to study trait anxiety in an experimental context is through the use of rat lines, selected according to contrasting phenotypes of fear and anxiety. It is not clear whether the behavioral differences between two contrasting rat lines in one given anxiety test are also present in others paradigms of state anxiety. Here, we examine the extent to which multiple anxiety traits generalize across selected animal lines originally selected for a single anxiety trait. We review the behavioral results available in the literature of eight rat genetic models of trait anxiety -namely Maudsley Reactive and Non-reactive rats, Floripa H and L rats, Tsukuba High and Low Emotional rats, High and Low Anxiety-related rats, High and Low Ultrasonic Vocalization rats, Roman High and Low Avoidance rats, Syracuse High and Low Avoidance rats, and Carioca High and Low Conditioned Freezing rats -across 11 behavioral paradigms of innate anxiety or aversive learning frequently used in the experimental setting. We observed both convergence and divergence of behavioral responses in these selected lines across the 11 paradigms. We find that predisposition for specific anxiety traits will usually be generalized to other anxiety provoking stimuli. However this generalization is not observed across all genetic models indicating some unique trait and state interactions. Genetic models of enhanced-anxiety related responses are beginning to help define how anxiety can manifest differently depending on the underlying traits and the current environmentally induced state. a r t i c l e i n f o

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Section: Problem Of Locomotor Activitymentioning

confidence: 99%

Behavioral evaluation of eight rat lines selected for high and low anxiety-related responses

Gomes

Hassan

Maisonnette

et al. 2013

Behavioural Brain Research

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“…For example, with regards the association between the amygdala and the fear responses, it has been reported that the basolateral but not the core center of amygdala is associated with fear responses induced by microinjection of HTR2C selective agonists (SB-242084, MK-212) in those brain areas in rats [Campbell and Merchant, 2003;de Mello Cruz et al, 2005]. Intriguingly, when a less specific agonist was administered (mCPP), a fear response was elicited as well, but mCPP triggered a latency to investigate new objects that was not associated with SB-242084 administration, suggesting that HTR2C plays a specific role in a fear reaction that does not dampen the explorative behavior.…”

Section: Htr2c Agonist-antagonist Challengesmentioning

confidence: 99%

Focus on HTR2C: A possible suggestion for genetic studies of complex disorders

Drago

Serretti

2009

American J of Med Genetics Pt B

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HTR2C is one of the most relevant and investigated serotonin receptors. Its role in important brain structures such as the midbrain, the lateral septal complex, the hypothalamus, the olfactory bulb, the pons, the choroid plexus, the nucleus pallidus, the striatum and the amygdala, the nucleus accumbens and the anterior cingulated gyrus candidate it as a promising target for genetic association studies. The biological relevance of these brain structures is reviewed by way of the focus on HTR2C activity, with a special attention paid to psychiatric disorders. Evidence from the genetic association studies that dealt with HTR2C is reviewed and discussed alongside the findings derived from the neuronatmic investigations. The reasons for the discrepancies between these two sets of reports are discussed. As a result, HTR2C is shown to play a pivotal role in many different psychiatric behaviors or psychiatric related disrupted molecular balances, nevertheless, genetic association studies brought inconsistent results so far. The most replicated association involve the feeding behavior and antipsychotic induced side effects, both weight gain and motor related: Cys23Ser (rs6318) and -759C/T (rs3813929) report the most consistent results. The lack of association found in other independent studies dampens the clinical impact of these reports. Here, we report a possible explanation for discrepant findings that is poorly or not at all usually considered, that is that HTR2C may exert different or even opposite activities in the brain depending on the structure analyzed and that mRNA editing activity may compensate possible genetically controlled functional effects. The incomplete coverage of the HTR2C variants is proposed as the best cost-benefit ratio bias to fix. The evidence of brain area specific HTR2C mRNA editing opens a debate about how the brain can differently modulate stress events, and process antidepressant treatments, in different brain areas. The mRNA editing activity on HTR2C may play a major role for the negative association results.

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“…Animal studies also suggest that serotonergic neurotransmission in the basolateral nuclear complex of the amygdala (BLC) plays a critical role in stress, anxiety, and depression, but the exact effects depend on the type of serotonin receptor activated (Zangrossi and Graeff, 1994;Graeff et al, 1996;Zangrossi et al, 1999;De Mello Cruz et al, 2005;Abrams et al, 2005;Inoue et al, 2004). The type 3 serotonin receptor (5-HT 3 R) is unique in that it is the only serotonin receptor that is a ligand-gated ion channel (Barns and Sharp, 1999;Chameau and van Hooft, 2006).…”

Section: Nih Public Accessmentioning

confidence: 99%

A novel subpopulation of 5-HT type 3A receptor subunit immunoreactive interneurons in the rat basolateral amygdala

Mascagni

McDonald

2007

Neuroscience

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The amygdalar basolateral nuclear complex (BLC) has very high levels of the type 3 serotonin receptor (5-HT 3 R). Previous studies have reported that 5-HT 3 R protein in the BLC is expressed in interneurons and that 5-HT 3 R mRNA is coexpressed with GABA and certain neuropeptides or calcium-binding proteins in these cells. However, there have been no detailed descriptions of the distribution of 5-HT 3 R+ neurons in the amygdala, and no quantitative studies of overlap of neurons expressing 5-HT 3 R protein with distinct interneuronal subpopulations in the BLC. The present investigation employed dual-labeling immunohistochemistry using antibodies to the 5-HT-3A receptor subunit (5-HT 3A R) and specific interneuronal markers to address these questions. These studies revealed that there was a moderate density of nonpyramidal 5-HT 3A R+ neurons in the BLC at all levels of the amygdala. In addition, immunostained cells were also seen in anterior portions of the cortical and medial nuclei. Although virtually all 5-HT 3A R+ neurons in the BLC were GABA+, very few expressed neuropeptide or calcium-binding protein markers for individual subpopulations. The main interneuronal marker expressed by 5-HT 3A R+ neurons was cholecystokinin (CCK), but only 8-16% of 5-HT 3 R+ neurons in the BLC, depending on the nucleus, were CCK+. Most of these CCK+/5-HT 3A R+ double-labeled neurons appeared to belong to the subpopulation of large type L CCK+ interneurons. Very few 5-HT 3A R+ neurons expressed calretinin, vasoactive intestinal peptide, or parvalbumin, and none expressed somatostatin or calbindin. Thus, the great majority of neurons expressing 5-HT 3A R protein appear to constitute a previously unrecognized subpopulation of GABAergic interneurons in the BLC. Keywordsserotonin; GABA; peptides; calcium-binding proteinsThe amygdala receives a robust serotonergic innervation from the dorsal raphe nucleus that targets all amygdalar nuclei, especially the basolateral nuclear complex (Moore et al., 1978;Steinbusch, 1981;Fallon and Ciofi, 1992;Sadikot and Parent, 1990;Abrams et al., 2005). Microdialysis studies indicate that there is increased serotonin (5-HT) release in the amygdala during behavioral arousal and stress (Kawahara et al., 1993;Rueter and Jacobs, 1996). In addition, certain genetic variations in human serotonin transporter and tryptophan hydroxylase genes, which presumably result in altered extracellular serotonin levels, are associated with *Correspondence to: Alexander Joseph McDonald, Telephone: 803-733-3378, Fax: 803-733-1523, E-mail: mcdonald@med.sc.edu. Section Editor: Charles Gerfen (Neuroanatomy) Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could aff...

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Behavioral effects of systemically administered MK-212 are prevented by ritanserin microinfusion into the basolateral amygdala of rats exposed to the elevated plus-maze

Abstract: MK-212 increases anxiety and decreases locomotor activity. The anxiogenic-like profile of 5-HT2 receptor activation is prevented by the blockade of 5-HT2 receptors within the BLA, which does not have an effect by itself upon basal anxiety levels triggered by the EPM.

Cited by 70 publications

References 83 publications

Behavioral evaluation of eight rat lines selected for high and low anxiety-related responses

Behavioral evaluation of eight rat lines selected for high and low anxiety-related responses

Focus on HTR2C: A possible suggestion for genetic studies of complex disorders

A novel subpopulation of 5-HT type 3A receptor subunit immunoreactive interneurons in the rat basolateral amygdala

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