5-HT7 Receptor Inhibition and Inactivation Induce Antidepressantlike Behavior and Sleep Pattern

Hedlund, Peter B.; Huitrón‐Reséndiz, Salvador; Henriksen, Steven J.; Sutcliffe, J. Gregor

doi:10.1016/j.biopsych.2005.05.012

Cited by 238 publications

(219 citation statements)

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“…Most importantly, this pattern was the opposite to that of drug-exposed animals. Given the influence of 5-HT7 in emotion (Hedlund et al, 2005) and learning (Meneses, 2004), the collapse of differences in the behavioral baseline of HR and LR rats after experience with the drug could be attributable to the inverse pattern of 5-HT7 gene expression. These findings warrant further investigation about a putative interaction between the 5-HT7 receptor and CCK-ergic system.…”

Section: Discussionmentioning

confidence: 99%

The CCK-system underpins novelty-seeking behavior in the rat: Gene expression and pharmacological analyses

2008

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Cholecystokinin (CCK) and its receptor CCK-2R have been shown to promote emotional responsivity and behavioral sensitization to psychostimulants in the rat. An animal model has been developed based on locomotor response to a novel inescapable environment. Animals exhibiting consistent differences in locomotor response to novelty have been termed as High and Low Responder rats (HR and LR respectively). This paradigm is deemed to model sensation-seeking, a personality trait closely associated with substance abuse. The present study provides genetic and pharmacological evidence that the CCK-ergic system modulates this behavior. Distinctive patterns of CCK-related gene expression in HR and LR animals occurred beyond the mesolimbic pathways. CCK gene expression was higher in hippocampus, amygdala, and prefrontal cortex, but lower in the ventral tegmental area of HR relative to LR rats. Levels of CCK-2R mRNA were more elevated in LR animals in some areas of the forebrain such as the prefrontal cortex, nucleus accumbens, and hippocampus. Additionally, CCK-2R blockade with the antagonist LY225.910 (0.5 mg/Kg) removed phenotype differences in sustained exploration of novel stimuli (i.e., a novel-object) in HR and LR rats exposed to an enriched open-field test series. Finally, CCK-2R blockade also altered M 2 and 5-HT 7 receptor gene expression in the mediodorsal thalamus (a strategic structure for corticothalamic trafficking) in a phenotype-dependent manner. Taken together, the findings reported here suggest that distinct CCK-ergic function may contribute to promoting individual differences in noveltyseeking behavior.

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Section: Discussionmentioning

confidence: 99%

The CCK-system underpins novelty-seeking behavior in the rat: Gene expression and pharmacological analyses

2008

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“…As well as affecting circadian rhythms, the age-related decrease in 5-HT 7 receptor mRNA expression in the cingulate cortex may be related to age-associated changes in memory or affective state, because these processes that have been shown to be regulated by the cingulate cortex and modulated by 5-HT 7 receptors (Frankland et al, 2004;Maviel et al, 2004;Caetano et al, 2006;Mayberg, 2006;Roberts et al, 2004;Hedlund et al, 2005;Guscott et al, 2005). For example, the cingulate cortex participates in the regulation of contextual fear conditioning (Frankland et al, 2004) and in the affective response to pain (Johansen et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…The 5-HT 7 receptor subtype, the most recently cloned of the serotonin receptor subtypes, modulates many physiological and behavioral functions, including circadian rhythms (Ehlen et al, 2001;Duncan et al, 2004;, rapid eye movement (REM) sleep (Hagan et al, 2000;Thomas et al, 2003;Monti and Jantos, 2006), body temperature (Hedlund et al, 2003), learning and memory (Roberts et al, 2004), and behavior (Guscott et al, 2005;Hedlund et al, 2005). For example, administration of the 5-HT 7 receptor-selective antagonists, SB-269970-A or DR-4004, to hamsters blocks phase advances of circadian locomotor activity rhythms induced by the serotonergic agonists, 8-OH-DPAT or 5-carboxamidotryptamine, demonstrating that pharmacological activation of 5-HT 7 receptors stimulates circadian phase resetting (Ehlen et al, 2001;Duncan et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…Also, administration of 5-HT 7 receptor-selective antagonists to guinea pigs or rats selectively decreases REM sleep, suggesting that endogenous serotonin acting at 5-HT 7 receptors exerts a tonic inhibition on REM sleep (Hagan et al, 2000;Thomas et al, 2003;Monti and Jantos, 2006). Furthermore, studies in mice have shown that deletion of the 5-HT 7 receptor gene impairs memory and learning (Roberts et al, 2004), reduces immobility in the Porsolt swim test, similar to antidepressants (Guscott et al, 2005;Hedlund et al, 2005), and inhibits hypothermia induced by 8-OH-DPAT (Hedlund et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Expression of 5-HT7 receptor mRNA in the hamster brain: Effect of aging and association with calbindin-D28K expression

Duncan

Franklin

2007

Brain Research

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Aging affects several processes modulated by the 5-HT 7 receptor subtype, including circadian rhythms, learning and memory, and depression. Previously, we showed that aging induces a decrease in the hamster dorsal raphe (DRN) in both 5-HT 7 receptor binding and circadian phase resetting responses to 8-OH-DPAT microinjection. To elucidate the mechanisms underlying the aging decrease in 5-HT 7 receptors, we investigated aging modulation of 5-HT 7 receptor mRNA expression in the DRN, brain regions afferent to the DRN, and brain regions regulating circadian rhythms or memory. In situ hybridization for 5-HT 7 receptor mRNA was performed on coronal sections prepared from the brains of young, middle-aged, and old male Syrian hamsters. 5-HT 7 receptor mRNA expression was quantified by densitometry of X-ray film autoradiograms. The results showed that aging did not significantly affect 5-HT 7 receptor mRNA expression in the DRN or most other brain regions examined, with the exception of the cingulate cortex and paraventricular thalamic nucleus. Within the suprachiasmatic nucleus, the site of the master circadian pacemaker in mammals, 5-HT 7 receptor mRNA expression was localized in a discrete subregion resembling the calbindin subnucleus previously described. A second experiment using adjacent tissue sections showed that 5-HT 7 receptor mRNA and calbindin mRNAs were concentrated in the same region of the SCN, and as well as in the same region of several other brain structures. The localization of 5-HT 7 receptors and calbindin mRNAs within the same regions suggests that proteins they encode may interact to modulate processes such as circadian timekeeping.

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“…In both the forced swim test and the tail suspension test, inactivation or blockade of the 5-HT 7 receptor lead to antidepressantlike behavior [7,13,35]. Furthermore, inactivation or pharmacological blockade of the 5-HT 7 receptor lead to changes in rapid eye movement sleep that are opposite to those seen in depression [8,13]. In addition, it has been shown that certain antidepressants might exert some of their effects by acting directly at the 5-HT 7 receptor [26].…”

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confidence: 99%

The 5-HT7 receptor influences stereotypic behavior in a model of obsessive-compulsive disorder

Hedlund

Sutcliffe

2007

Neuroscience Letters

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The 5-HT 7 receptor has been suggested as a new putative target for the treatment of neuropsychiatric disorders, especially depression. This hypothesis is based on the finding that antidepressant drugs have relatively high affinity for the 5-HT 7 receptor, and that inactivation or blockade of the receptor leads to an antidepressant-like profile in behavioral models and sleep parameters. Obsessivecompulsive disorder is also believed to involve the serotonergic system and is treated using antidepressants, thus it is of interest to study the possible role of the 5-HT 7 receptor in this disorder. We have evaluated the effect of inactivation or pharmacological blockade of the 5-HT 7 receptor in three mouse behavioral models that are believed to mimic some of the stereotypic aspects of obsessive-compulsive disorder. In the most well established behavioral model, marble burying, both inactivation and blockade of the 5-HT 7 receptor reduced stereotypic behavior in that the number of marbles buried decreased. In two newer, less well characterized models, head dipping and plasticmesh screen chewing, there was no difference between wild-type mice and mice lacking the 5-HT 7 receptor. Taken together the data confirms and expands on previous findings that the 5-HT 7 receptor is of importance for behaviors affected by antidepressants, and suggests that the 5-HT 7 receptor might be of relevance as a target for the treatment of obsessive-compulsive disorder. Keywordsserotonin; marble burying; head dipping; screen chewing; SB-269970The 5-HT 7 receptor, one of the most recently discovered receptors for serotonin [12], has been found to modulate behaviors affected by antidepressant drugs. In both the forced swim test and the tail suspension test, inactivation or blockade of the 5-HT 7 receptor lead to antidepressantlike behavior [7,13,35]. Furthermore, inactivation or pharmacological blockade of the 5-HT 7 receptor lead to changes in rapid eye movement sleep that are opposite to those seen in depression [8,13]. In addition, it has been shown that certain antidepressants might exert some of their effects by acting directly at the 5-HT 7 receptor [26].Obsessive-compulsive disorder (OCD) is a debilitating disease with an overall prevalence of close to 1 % [15]. There is strong evidence in support of a significant role for 5-HT in OCD and antidepressant drugs, mainly selective serotonin reuptake inhibitors (SSRIs), are the pharmacological treatment of choice for OCD [4,15]. However, as many as 40 % of patients do not respond to currently available treatment options [15], so continued research is necessary. 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 affect the c...

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5-HT7 Receptor Inhibition and Inactivation Induce Antidepressantlike Behavior and Sleep Pattern

Cited by 238 publications

References 50 publications

The CCK-system underpins novelty-seeking behavior in the rat: Gene expression and pharmacological analyses

The CCK-system underpins novelty-seeking behavior in the rat: Gene expression and pharmacological analyses

Expression of 5-HT7 receptor mRNA in the hamster brain: Effect of aging and association with calbindin-D28K expression

The 5-HT7 receptor influences stereotypic behavior in a model of obsessive-compulsive disorder

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