Sucrose intake and fasting glucose levels in 5-HT1A and 5-HT1B receptor mutant mice

Bechtholt, Anita J.; Smith, Karen; Gaughan, Stephanie; Lucki, Irwin

doi:10.1016/j.physbeh.2007.11.006

Cited by 38 publications

(25 citation statements)

References 27 publications

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“…Furthermore, we found increased extracellular serotonin levels in the ventral hippocampus of ePet-Cre+ mice in response to SSRI administration, suggesting a functional role for 5-HT 1B autoreceptors in the regulation of serotonin release in the hippocampus. These increases in serotonin levels and antidepressant-like phenotypes have been seen previously in the ubiquitous 5-HT 1B R KO (Bechtholt et al, 2008;Jones and Lucki, 2005;Knobelman et al, 2001;Mayorga et al, 2001), but importantly, our genetic model allowed the dissociation of the role of 5-HT 1B autoreceptors from heteroreceptors. This advancement is significant since pharmacological dissection via local infusion of antagonists or agonists is not possible given the terminal localization of 5-HT 1B autoreceptors throughout the brain (McDevitt and Neumaier, 2011).…”

Section: Discussionsupporting

confidence: 74%

“…Additionally, 5-HT 1B R knockout mice have increased levels of 5-HT, compared with wild-type mice, following administration of a selective serotonin reuptake inhibitor (SSRI) (Knobelman et al, 2001;Malagie et al, 2001). Behaviorally, an absence of all 5-HT 1B Rs in mice results in decreased depressive behaviors (Bechtholt et al, 2008;Jones and Lucki, 2005;Mayorga et al, 2001). However, these studies were not able to directly distinguish the contribution of autoreceptors from the rest of 5-HT 1B Rs.…”

Section: Introductionmentioning

confidence: 99%

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A Lack of Serotonin 1B Autoreceptors Results in Decreased Anxiety and Depression-Related Behaviors

Nautiyal

Tritschler

Ahmari

et al. 2016

Neuropsychopharmacol

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The effects of serotonin (5-HT) on anxiety and depression are mediated by a number of 5-HT receptors, including autoreceptors that act to inhibit 5-HT release. While the majority of anxiety and depression-related research has focused on the 5-HT 1A receptor, the 5-HT 1B receptor has a lesser known role in modulating emotional behavior. 5-HT 1B receptors are inhibitory GPCRs located on the presynaptic terminal of both serotonin and non-serotonin neurons, where they act to inhibit neurotransmitter release. The autoreceptor population located on the axon terminals of 5-HT neurons is a difficult population to study due to their diffuse localization throughout the brain that overlaps with 5-HT 1B heteroreceptors (receptors located on non-serotonergic neurons). In order to study the contribution of 5-HT 1B autoreceptors to anxiety and depression-related behaviors, we developed a genetic mouse model that allows for selective ablation of 5-HT 1B autoreceptors. Mice lacking 5-HT 1B autoreceptors displayed the expected increases in extracellular serotonin levels in the ventral hippocampus following administration of a selective serotonin reuptake inhibitor. In behavioral studies, they displayed decreased anxietylike behavior in the open field and antidepressant-like effects in the forced swim and sucrose preference tests. These results suggest that strategies aimed at blocking 5-HT 1B autoreceptors may be useful for the treatment of anxiety and depression.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

A Lack of Serotonin 1B Autoreceptors Results in Decreased Anxiety and Depression-Related Behaviors

Nautiyal

Tritschler

Ahmari

et al. 2016

Neuropsychopharmacol

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“…Interestingly, mice bearing a constitutive deletion of 5-HT1B display aggressive behavior and reduced anxiety relative to WT, but do not display anhedonia (28,31). Furthermore, mice with constitutive loss of either 5-HT1A or 5-HT1B did not display an impairment in preference to sucrose consumption (41). It is likely that 5-HT1B plays opposing roles in different populations of neurons in mediating pleasure response.…”

Section: Discussionmentioning

confidence: 99%

Opposing roles for serotonin in cholinergic neurons of the ventral and dorsal striatum

Virk

Sagi

Medrihan

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Little is known about the molecular similarities and differences between neurons in the ventral (vSt) and dorsal striatum (dSt) and their physiological implications. In the vSt, serotonin [5-Hydroxytryptamine (5-HT)] modulates mood control and pleasure response, whereas in the dSt, 5-HT regulates motor behavior. Here we show that, in mice, 5-HT depolarizes cholinergic interneurons (ChIs) of the dSt whereas hyperpolarizing ChIs from the vSt by acting on different 5-HT receptor isoforms. In the vSt, 5-HT1A (a postsynaptic receptor) and 5-HT1B (a presynaptic receptor) are highly expressed, and synergistically inhibit the excitability of ChIs. The inhibitory modulation by 5-HT1B, but not that by 5-HT1A, is mediated by p11, a protein associated with major depressive disorder. Specific deletion of 5-HT1B from cholinergic neurons results in impaired inhibition of ACh release in the vSt and in anhedonic-like behavior.5-HT1A | 5-HT1B | cholinergic interneurons | ventral striatum | TRAP C holinergic interneurons (ChIs) represent only 1-2% of all striatal neurons (1). Despite their low abundance, ChIs play a major role in striatal function, by modulating both inputs to and outputs from spiny projection neurons (SPNs) (2). In the ventral striatum (vSt), ChIs are thought to play a major role in mediating reward, motivation, food intake, and hedonic behavior, whereas ChIs of the dorsal striatum (dSt) are implicated in motor behavior and action selection (3-5). Despite their functional differences, only a few morphological differences between vSt and dSt ChIs have been demonstrated, but no molecular differences between these two populations have been reported (6).Serotonin [5-Hydroxytryptamine (5-HT)] signaling in the striatum has long been implicated in modulating locomotion as well as in mood control (7-9). Striatal 5-HT levels are high, and multiple 5-HT receptors (5-HTRs) are thought to mediate the function of 5-HT in these circuits (7, 10). In dSt ChIs, several 5-HTRs (5-HT7, 5-HT6, and 5-HT2) have been reported to induce membrane depolarization (11,12), but the role of 5-HT signaling in vSt ChIs and its implication for mood regulation are poorly understood. To elucidate the role of 5-HT in vSt ChIs, we used electrophysiological recordings, optogenetics, and cell type-specific gene expression analysis. We demonstrate that 5-HT1A and 5-HT1B synergistically inhibit the function of vSt ChIs. The effect of activation of 5-HT1B, but not that of 5-HT1A, is mediated by p11. Furthermore, deletion of 5-HT1B from cholinergic neurons resulted in a loss of pleasure response (anhedonia), a core symptom of major depressive disorder. ResultsOpposite Effects of 5-HT on Cell Excitability Between vSt ChIs and dSt ChIs. To investigate the effect of 5-HT on ChIs from the vSt and dSt, we carried out electrophysiological recordings from visually identified neurons in acute brain slices. To identify ChIs, we used translating ribosome affinity purification (TRAP) mice expressing a GFP-tagged ribosomal protein, L10a, under the choline acetyltrans...

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“…A knockout of this receptor leads to reduced food intake [41]. Very likely, the knockout will diminish or eliminate the negative somatodendritic feedback and thus increase 5-HT release that will induce hypophagia via postsynaptic 5-HT2C and 5-HT1B receptor activation, although no change in habitual feeding in 5-HT1A receptor knockout mice has been displayed in another study [139].…”

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confidence: 97%

Serotonin controlling feeding and satiety

Voigt

Fink

2015

Behavioural Brain Research

270

167

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Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes. This approach also required the availability of receptor ligands of different selectivity, and behavioural techniques had to be developed simultaneously which allow differentiating between unspecific pharmacological effects of these ligands and 'true' 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 IntroductionWhat are the behavioural and physiological mechanisms that promote satiety? How is satiety defined? Satiety can be seen as a behavioural state which arises from food consumption and suppresses the initiation of eating for a particular period of time [1]. This description alone suggests a high degree of complexity as peripheral post-ingestive and post-absorptive signals need to be relayed to the brain where they are integrated with other signals to produce (or not) the behavioural state called satiety. The state of satiety is brought about a process called satiation, where sensory, cognitive and early post-ingestive mechanisms bring feeding to a halt and thus stopping a meal. Promoting satiation alone must not necessarily lead to reduced total food intake as the frequency of meals could be increased subsequently. Many peripheral and brain mechanisms have been identified that are involved in the expression satiety and it has been suggested that serotonin accelerates satiation and prolongs satiety [2]. In the following, we will review the role of serotonin in satiety in more detail 1 . The reader will see that, despite immense progress made during the last years, the field is still far from being resolved.As serotonin (5-Hydroxytryptamine; 5-HT) is a phylogenetically old neurotransmitter, various functions had time to evolve in different phyla, but maybe also in different species. 5-HT receptors exist in animal cells for millions of years and they are as old as adrenoreceptors ore some peptide receptors, possibly even older [5,6]. Even in invertebrates such as molluscs (Aplysia californica) and annelids (Hirudo medicinalis), 5-HT might functionally be related to food intake [7]. 5-HT is involved in feeding even in the honeybee where it has separate effects in the gut and in the insect brain [8]. In general, however, 5-HT seems rather to be involved in appetitive behaviours in invertebrates whereas it has more of a satiating effect in vertebrates [9]. In general, 5-HT neurons seem to be more extensively distributed throughout the body in lower animals than in higher animals including mammals where 5-HT neurones...

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Sucrose intake and fasting glucose levels in 5-HT1A and 5-HT1B receptor mutant mice

Cited by 38 publications

References 27 publications

A Lack of Serotonin 1B Autoreceptors Results in Decreased Anxiety and Depression-Related Behaviors

A Lack of Serotonin 1B Autoreceptors Results in Decreased Anxiety and Depression-Related Behaviors

Opposing roles for serotonin in cholinergic neurons of the ventral and dorsal striatum

Serotonin controlling feeding and satiety

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