Parabrachial infusion of d-fenfluramine reduces food intake

Simansky, Kenny J.; Nicklous, Danielle M.

doi:10.1016/s0091-3057(01)00740-7

Cited by 46 publications

(40 citation statements)

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“…9 Activation of 5-HT 1A receptors increases food intake, whereas activation of 5-HT 1B, 2A and 2C receptors attenuates feeding behavior in mice. [31][32][33] The 5-HTT ko mice have increased extracellular and decreased intracellular concentrations of 5-HT in the brain 11,34 and altered expression of some 5-HT receptor subtypes, 35 such that a difference in food intake compared with WT mice might have been expected. However, food intake was unaltered in 5-HTT ko mice of any age.…”

Section: Discussionmentioning

confidence: 99%

Lack of the serotonin transporter in mice reduces locomotor activity and leads to gender-dependent late onset obesity

et al. 2010

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Objective: Mice deficient of the serotonin transporter (5-HTT ko) mice have a reduced brain serotonin content and develop lateonset obesity. To elucidate the pathophysiology of this obesity, we analyzed the expression of the interrelated weight-regulatory molecules: brain-derived neurotrophic factor (BDNF) and leptin receptor (LR) in brain areas associated with nutrition and activity. Research Design and Methods: We investigated feeding behavior, physical activity and metabolic parameters of 5-HTT ko and wild-type mice and measured the expression of BDNF and LR in brain areas associated with nutrition and activity using quantitative real-time PCR. The influence of age, gender and fasting was analyzed. Results: Male 5-HTT ko mice developed obesity without hyperphagia from the age of 5 months. Physical activity was reduced in old male, but not old female, 5-HTT ko mice. The BDNF gene expression in frontal cortex was elevated in young, but reduced in old 5-HTT ko mice. Fasting failed to increase the BDNF gene expression in frontal cortex of young 5 HTT ko mice and in the hypothalamus in old 5-HTT ko mice. The fasting-induced hypothalamic increase of LR was absent in both young and old 5-HTT ko mice. Conclusions: We propose that low brain serotonin level due to the 5-HTT ko genotype leads to reduced physical activity and low BDNF, which together with the lack of fasting-induced hypothalamic BDNF and LR production results in late-onset obesity. Although lack of the 5-HTT is a genetic vulnerability factor for obesity, female gender is protective.

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Section: Discussionmentioning

confidence: 99%

Lack of the serotonin transporter in mice reduces locomotor activity and leads to gender-dependent late onset obesity

et al. 2010

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“…These pharmacological data, therefore, provide direct support for the parabrachial region as a locus within the brain where opioids subserve the distributed neural network modulating normal feeding behavior. Other studies have implicated serotonin (48,80), GABA (32,82), neuropeptide FF (66,79), and perhaps CCK (85). The functions mediated by each of these neuromediators and by their interactions in the regulatory physiology of the PBN are inviting targets for investigation.…”

Section: Discussionmentioning

confidence: 99%

“…In the lateral region of this nucleus (LPBN), these include mediating 1) feeding elicited by several antimetabolites (12,28,33,87); 2) hypophagic actions of CCK (85,88); 3) serotonergic inhibition of salt appetite (59) and feeding (47,80); 4) hyperphagic actions of a benzodiazepine agonist (32,82); and 5) sensory and associative mechanisms of the learning of both taste aversions and preferences (27,73,76).…”

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confidence: 99%

An orexigenic role for μ-opioid receptors in the lateral parabrachial nucleus

Wilson

Nicklous

Aloyo

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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. The pontine parabrachial nucleus (PBN) has been implicated in regulating ingestion and contains opioids that promote feeding elsewhere in the brain. We tested the actions of the selective -opioid receptor (-OR) agonist [D-Ala 2 ,N-Me-Phe 4 ,Gly 5 -ol]enkephalin (DAMGO) in the PBN on feeding in male rats with free access to food. Infusing DAMGO (0.5-4.0 nmol/0.5 l) into the lateral parabrachial region (LPBN) increased food intake. The hyperphagic effect was anatomically specific to infusions within the LPBN, dose and time related, and selective for ingestion of chow compared with (nonnutritive) kaolin. The nonselective opioid antagonist naloxone (0.1-10.0 nmol intra-PBN) antagonized DAMGO-induced feeding, with complete blockade by 1.0 nmol and no effect on baseline. The highly selective -opioid antagonist D-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; 1.0 nmol) also prevented this action of DAMGO, but the -antagonist nor-binaltorphimine did not. Naloxone and CTAP (10.0 nmol) decreased intake during scheduled feeding. Thus stimulating -ORs in the LPBN increases feeding, whereas antagonizing these sites inhibits feeding. Together, our results implicate -ORs in the LPBN in the normal regulation of food intake.feeding; hyperphagia; DAMGO; naloxone; CTAP STIMULATING ANY OF THE SUBTYPES of opioid receptors (ORs; , , ␦) or the related orphan receptor for nociceptin increases food intake in mammals (6,24,26,71,77). The orexigenic effects of these treatments are evident particularly in settings using preferred foods for the test diet (e.g., 39, 94, 95), although consumption of standard chow is also enhanced (9, 72). Conversely, drugs that block ORs reduce food intake (11,16,41,49). This hypophagia may occur especially under conditions when opioid pathways are highly activated (53). The data, therefore, suggest that opioid peptides play roles in the physiological control of feeding.The anatomic loci subserving opioidergic feeding are distributed widely throughout the brain. Attention has focused on the nucleus accumbens (NAC) and the rest of the ventral striatum as a critical region (9,72,94,95). Infusing opioid agonists into the ventral tegmental area of the midbrain, which projects onto the ventral striatum, also stimulates feeding (45, 67); this circuitry is consistent with the view assigning a broader role for opioids to support positive affect and appetitive reward (39, 70). Another (probably integrated) circuit is defined by observations that opioid stimulation of the paraventricular hypothalamic nucleus (21, 22) The parabrachial nucleus (PBN) of the pons has bidirectional communication with the PVN, central nucleus of the amygdala, and NTS (19,29,61,62). The multiple subnuclei of the PBN sort afferent input from second-order sensory neurons originating in the NTS and spinal cord (38,83) and distribute the information to rostral targets (19,36,37,68). This sensory processing includes neurotransmission underlying gustatory and visceral function and their convergence (8,30,38).It is logical, then, that the PBN has been imp...

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“…The parabrachial nucleus has been identified, therefore, as a functional unit that integrates feeding related signals from several brain regions [211,213] and could possibly provide a functional link between hypothalamic and hindbrain mechanisms of 5-HT mediated satiety. 5-HT1B receptor activation in the parabrachial nucleus reduces food intake [214] and the hypophagic effect of fenfluramine in the parabrachial nucleus requires 5-HTB receptor activation [215].…”

Section: Brain Mechanisms Of Serotonergic Satietymentioning

confidence: 99%

Serotonin controlling feeding and satiety

Voigt

Fink

2015

Behavioural Brain Research

257

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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Parabrachial infusion of d-fenfluramine reduces food intake

Cited by 46 publications

References 59 publications

Lack of the serotonin transporter in mice reduces locomotor activity and leads to gender-dependent late onset obesity

Lack of the serotonin transporter in mice reduces locomotor activity and leads to gender-dependent late onset obesity

An orexigenic role for μ-opioid receptors in the lateral parabrachial nucleus

Serotonin controlling feeding and satiety

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