Infusion of the serotonin 1B (5-HT 1B ) agonist CP-93,129 into the parabrachial nucleus potently and selectively reduces food intake in rats

Lee, M. D.; Aloyo, Vincent J.; Fluharty, Steven J.; Simansky, Kenny J.

doi:10.1007/s002130050570

Cited by 65 publications

(48 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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%

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

Self Cite

View full text Add to dashboard Cite

. 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...

show abstract

Section: Discussionmentioning

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…Hence, a highly selective HTR1B agonist, CP93129 dihydrochloride [23], was applied for further examination. CP93129 could closely resemble the effects of 5-HT on the activation of kinases in human endothelial cells (Fig.…”

Section: -Ht Receptor 1b Mediates Activation Of Signaling Kinasesmentioning

confidence: 99%

Serotonin activates angiogenic phosphorylation signaling in human endothelial cells

Zamani

2012

FEBS Letters

View full text Add to dashboard Cite

a b s t r a c tSerotonin, a known neurotransmitter, also functions as an angiokine to promote angiogenesis. The majority of serotonin in the human body is stored in platelets, and platelet aggregation leads to significant release of serotonin in thrombotic tumor environment. We have investigated serotonin signaling in human endothelial cells. Through G-protein-coupled receptors, serotonin at physiologically relevant concentrations activated Src/PI3K/AKT/mTOR/p70S6K phosphorylation signaling, and this activation was similar to that seen with VEGF. This finding provides insight into the overlapping angiogenic signaling pathways stimulated by serotonin in tumor environment, and suggests one of the mechanisms underlying resistance to current VEGF-targeting antiangiogenic therapy against cancer.

show abstract

“…), but responded normally to the compound CP-93129, which targets brain 5-HT 1B receptors (Fig. 3a, d) 19 . These ®ndings support the hypothesis that OEA reduces food intake by acting at a peripheral site and that sensory ®bres are required for this effect.…”

mentioning

confidence: 94%

An anorexic lipid mediator regulated by feeding

Fonseca

Navarro

Gómez

et al. 2001

Nature

646

767

View full text Add to dashboard Cite

Oleylethanolamide (OEA) is a natural analogue of the endogenous cannabinoid anandamide. Like anandamide, OEA is produced in cells in a stimulus-dependent manner and is rapidly eliminated by enzymatic hydrolysis, suggesting a function in cellular signalling 1. However, OEA does not activate cannabinoid receptors and its biological functions are still unknown 2. Here we show that, in rats, food deprivation markedly reduces OEA biosynthesis in the small intestine. Administration of OEA causes a potent and persistent decrease in food intake and gain in body mass. This anorexic effect is behaviourally selective and is associated with the discrete activation of brain regions (the paraventricular hypothalamic nucleus and the nucleus of the solitary tract) involved in the control of satiety. OEA does not affect food intake when injected into the brain ventricles, and its anorexic actions are prevented when peripheral sensory fibres are removed by treatment with capsaicin. These results indicate that OEA is a lipid mediator involved in the peripheral regulation of feeding

show abstract

Infusion of the serotonin 1B (5-HT 1B ) agonist CP-93,129 into the parabrachial nucleus potently and selectively reduces food intake in rats

Cited by 65 publications

References 19 publications

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

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

Serotonin activates angiogenic phosphorylation signaling in human endothelial cells

An anorexic lipid mediator regulated by feeding

Contact Info

Product

Resources

About