Male and female 5-HT1B receptor knockout mice have higher body weights than wildtypes

Bouwknecht, J.Adriaan; Gugten, Jan van der; Hijzen, Theo H.; Maes, R. A. A.; Hen, René; Olivier, Berend

doi:10.1016/s0031-9384(01)00589-3

Cited by 92 publications

(55 citation statements)

References 66 publications

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“…In contrast, absolute food intake in these mice was increased when intake measures were not related to body weight. As a consequence, 5-HT1B receptor deletion led to increased body weight, but leptin levels remained unchanged and despite the increased body weight these mice were not deemed obese [96]. In line with the aforementioned pharmacological findings, both fenfluramine and the 5-HT1A/B agonist RU-24969 lost their hypophagic effects in these mice, further supporting the role of 5-HT1B receptor in satiety [73,95].…”

Section: Brain 5-ht and Satietysupporting

confidence: 58%

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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Section: Brain 5-ht and Satietysupporting

confidence: 58%

Serotonin controlling feeding and satiety

Voigt

Fink

2015

Behavioural Brain Research

270

167

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“…Accordingly, animals lacking the 5-HT 1B receptor consumed more food than their wild-type counterparts especially as they aged, although increased intake remained proportional to their body weight [e.g. 5]. Pharmacological stimulation of 5-HT 1A receptors using 8-OH-DPAT has been reported to either increase [e.g.…”

Section: Introductionmentioning

confidence: 99%

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

Bechtholt

Smith

Gaughan

et al. 2008

Physiology & Behavior

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Serotonin (5-HT) 1A and 5-HT 1B receptors have been implicated in the incidence and treatment of depression in part through the examination of animals lacking these receptors. Although these receptors have been repeatedly implicated in ingestive behavior there is little information about how 5-HT 1A and 5-HT 1B receptor mutant mice react to solutions of varying palatability. In the present experiment male and female 5-HT 1A and 5-HT 1B mutant and wild-type mice were presented with increasing concentrations of sucrose using a two-bottle choice procedure. In addition fasting blood glucose levels were assessed. Both male and female 5-HT 1B mutant mice drank more sucrose than WT mice but also consumed more water. Female, but not male, 5-HT 1A mutant mice similarly showed increased sucrose consumption, but did not demonstrate increased consumption of water. In addition, the pattern of increased sucrose consumption over genotype and sex was related to fasting blood glucose concentrations such that levels in male 5-HT 1B mutant mice were reduced relative to wild-type and 5-HT 1A mutant males, but similar to those of females. The findings in 5-HT 1B mutant mice emphasize the role of the 5-HT 1B receptor in regulating ingestive behavior, whereas female sex hormones and 5-HT 1A receptors may interact to alter sucrose consumption in 5-HT 1A mutant mice. In addition, these findings may have implications for the role of these receptors in the incidence and treatment of depression since the intake of sucrose has been used as an index of anhedonia in animal models of depression and antidepressant efficacy.

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“…Two earlier studies have reported that male 5-HT 1B receptor-null mice are overweight and consume a higher amount of food than wild-type mice (Brunner et al, 1999;Bouwknecht et al, 2001). However, the validity of the results was a matter of debate because wild-type and null mice were obtained from independent lines (Bouwknecht et al, 2001).…”

Section: Similar Baseline Food Intake and Body Weight Of 5-ht 1b Recementioning

confidence: 99%

Section: Similar Baseline Food Intake and Body Weight Of 5-ht 1b Recementioning

confidence: 99%

“…However, the validity of the results was a matter of debate because wild-type and null mice were obtained from independent lines (Bouwknecht et al, 2001). Therefore, we used homozygote offspring from heterozygote breeding pairs (Animal section) in order to avoid indirect effects of parental care behavioral responses, as discussed by Bouwknecht et al (2001). No difference in either baseline food intake or body weight was detected between wild-type and 5-HT 1B receptor-null mice for the habituation period or following a 24 h period of food deprivation (data not shown), as reported previously (Lucas et al, 1998 MDMA produced a profound reduction in food intake for 1 h in starved wild-type mice, as compared with NaCltreated wild-type mice (À77%, Figure 1a).…”

Section: Similar Baseline Food Intake and Body Weight Of 5-ht 1b Recementioning

confidence: 99%

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3,4-N-Methlenedioxymethamphetamine-Induced Hypophagia is Maintained in 5-HT1B Receptor Knockout Mice, but Suppressed by the 5-HT2C Receptor Antagonist RS102221

Conductier

Crosson

Hen

et al. 2005

Neuropsychopharmacol

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3,4-Methylenedioxy-N-methamphetamine (MDMA or 'ecstasy') is a psychoactive substance, first described as an appetite suppressant in humans, inducing side effects and even death. MDMA increases serotonin (5-HT) levels, and 5-HT inhibits food intake, but the 5-HT receptors involved in MDMA-induced changes in feeding behavior are unknown. We examined whether a systemic MDMA injection would reduce the physiological drive to eat in starved mice and tested if the inactivation of 5-HT 1B or 5-HT 2C receptors could restore this response. Our results indicate that in starved mice, MDMA (10 mg/kg) provoked an initial hypophagia for 1 h (À77%) followed by a period of hyperphagia (studied between 1 and 3 h). This biphasic feeding behavior due to MDMA treatment was maintained in 5-HT 1B receptornull mice or in animals treated with the 5-HT 1B/1D receptor antagonist GR127935 (3 or 10 mg/kg). In contrast, MDMA-induced hypophagia (for the first 1 h period) was suppressed when combined with the 5-HT 2C receptor antagonist RS102221 (2 mg/kg). However, RS102221 did not alter MDMA-induced hyperphagia (for the 1-3 h period) but did exert a stimulant effect, when administered alone, during that period. We have previously shown that MDMA or 5-HT 1A/1B receptor agonist RU24969 fails to stimulate locomotor activity in 5-HT 1B receptor-null mice. Our present data indicate that the 5-HT 2C receptor antagonist RS102221 suppresses MDMA-induced hyperlocomotion. These findings provide the first evidence that the inactivation of 5-HT 2C receptors may reduce hypophagia and motor response to MDMA, while a genetic deficit or pharmacological inactivation of 5-HT 1B receptors was insufficient to alter the feeding response to MDMA.

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Male and female 5-HT1B receptor knockout mice have higher body weights than wildtypes

Cited by 92 publications

References 66 publications

Serotonin controlling feeding and satiety

Serotonin controlling feeding and satiety

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

3,4-N-Methlenedioxymethamphetamine-Induced Hypophagia is Maintained in 5-HT1B Receptor Knockout Mice, but Suppressed by the 5-HT2C Receptor Antagonist RS102221

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