Local perfusion of mCPP into ventromedial hypothalamic nucleus, but not into lateral hypothalamic area and frontal cortex, inhibits food intake in rats

Hikiji, Katsuhito; Inoue, Koki; Iwasaki, Shinichi; Ichihara, Kyuichiro; Kiriike, Nobuo

doi:10.1007/s00213-003-1735-0

Cited by 21 publications

(14 citation statements)

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“…Many biological agents given into the VMH have been demonstrated to affect feeding. Food intake is inhibited by administration of histamine (4,47), glucagon-like peptide 1 (70), serotonin agonists (25), urocortin (58), CCK (79), leptin (51), and insulin (78), whereas thyroid hormone (3,5,3Ј-triiodothyronine) (40), GABA or GABA agonists (32,34,35), norepinephrine (73), orexin (74), and NPY induce feeding after administration into the VMH (5,9,24,31,43,56,76).…”

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confidence: 99%

Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake

Wang

Bomberg²,

Levine³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Recent studies show that brainderived neurotrophic factor (BDNF) decreases feeding and body weight after peripheral and ventricular administration. BDNF mRNA and protein, and its receptor TrkB, are widely distributed in the hypothalamus and other brain regions. However, there are few reports on specific brain sites of actions for BDNF. We evaluated the effect of BDNF, given into the ventromedial nucleus of the hypothalamus (VMH), on normal and deprivation-and neuropeptide Y (NPY)-induced feeding behavior and body weight. BDNF injected unilaterally or bilaterally into the VMH of food-deprived and nondeprived rats significantly decreased feeding and body weight gain within the 0-to 24-h and the 24-to 48-h postinjection intervals. Doses effectively producing inhibition of feeding behavior did not establish a conditioned taste aversion. BDNF-induced feeding inhibition was attenuated by pretreatment of the TrkB-Fc fusion protein that blocks binding between BDNF and its receptor TrkB. VMH-injected BDNF significantly decreased VMH NPY-induced feeding at 1, 2, and 4 h after injection. In summary, BDNF in the VMH significantly decreases food intake and body weight gain, by TrkB receptor-mediated actions. Furthermore, the anorectic effects of BDNF in this site appear to be mediated by NPY. These data suggest that the VMH is an important site of action for BDNF in its effects on energy metabolism. food intake; body weight THE VENTROMEDIAL NUCLEUS OF THE HYPOTHALAMUS (VMH) is a brain area important to the regulation of energy metabolism. Early studies indicated that VMH lesions resulted in hyperphagia and obesity (28,38,66), whereas electrical stimulation of the VMH immediately suppressed feeding and induced lipolysis (65). Glucose-sensing neurons (7,27,55,74,75) and receptors for neuropeptides important to energy metabolism have been identified in the VMH, including leptin (13,17,20,22,51), melanocortin (26), neuropeptide Y (NPY) (43), corticotrophin-releasing hormone (49), CCK (12), insulin (33), and orexin (44) receptors. Many biological agents given into the VMH have been demonstrated to affect feeding. Food intake is inhibited by administration of histamine (4, 47), glucagon-like peptide 1 (70), serotonin agonists (25), urocortin (58), CCK (79), leptin (51), and insulin (78), whereas thyroid hormone (3,5,3Ј-triiodothyronine) (40), GABA or GABA agonists (32,34,35), norepinephrine (73), orexin (74), and NPY induce feeding after administration into the VMH (5,9,24,31,43,56,76).Anatomically, the VMH receives inputs from regions important to the regulation of energy metabolism, including the hypothalamic arcuate nucleus (ARC) (2, 14, 23), lateral hypothalamus (18, 67, 80), amygdala (45, 50), and lateral septum. The VMH also projects to ARC (77), paraventricular nucleus (PVN) (42, 52), lateral hypothalamus (72, 80), dorsomedial nucleus of the hypothalamus (46, 80), amygdala (6, 68), lateral septum (68), ventral tegmental area (68), nucleus accumbens (6), and nucleus of the solitary tract (6). These behavioral and neuroanatom...

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confidence: 99%

Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake

Wang

Bomberg²,

Levine³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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“…5-HT 2C receptors are reported to be present in both of these regions (Abramowski et al, 1995;Clemett et al, 2000) and, thus, the modulation may be a direct effect. Indeed, mCPP administered directly into the ventromedial hypothalamic nucleus inhibits feeding in rats (Hikiji et al, 2004).…”

Section: Discussionmentioning

confidence: 98%

“…, 2000) and, thus, the modulation may be a direct effect. Indeed, mCPP administered directly into the ventromedial hypothalamic nucleus inhibits feeding in rats (Hikiji et al. , 2004).…”

Section: Discussionmentioning

confidence: 99%

5‐HT_2C antagonism blocks blood oxygen level‐dependent pharmacological‐challenge magnetic resonance imaging signal in rat brain areas related to feeding

Stark

McKie

Davies

et al. 2008

Eur J of Neuroscience

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In this study, pharmacological-challenge magnetic resonance imaging was used to further characterize the central action of serotonin on feeding. In both feeding and pharmacological-challenge magnetic resonance imaging experiments, we combined 5-HT(1B/2C) agonist m-chlorophenylpiperazine (mCPP) challenge with pre-treatment with the selective 5-HT(1B) and 5-HT(2C) receptor antagonists, SB 224289 (2.5 mg/kg) and SB 242084 (2 mg/kg), respectively. Subcutaneous injection of mCPP (3 mg/kg) completely blocked fast-induced refeeding in freely behaving, non-anaesthetized male rats, an effect that was not modified by the 5-HT(1B) receptor antagonist but was partially reversed by the 5-HT(2C) receptor antagonist. mCPP alone induced both positive and negative blood oxygen level-dependent (BOLD) responses in the brains of anaesthetized rats, including in the limbic system and basal ganglia. Overall, the 5-HT(2C) antagonist SB 242084 reversed the effects elicited by mCPP, whereas the 5-HT(1B) antagonist SB 224289 had virtually no impact. SB 242084 eliminated BOLD signal in nuclei associated with the limbic system and diminished activation in basal ganglia. In addition, BOLD signal was returned to baseline levels in the cortical regions and cerebellum. These results suggest that mCPP may reduce food intake by acting specifically on brain circuits that are modulated by 5-HT(2C) receptors in the rat.

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“…This receptor subtype is mainly expressed in the central nervous system (CNS) [148], and the presence of 5-HT 2C receptors in the hypothalamus is believed to play a key role in the serotonergic control of appetite and feeding. For example, many nonselective 5HT 2C receptor agonists, including m-chlorophenylpiperazine (m-CPP), are known to reduce food intake and induce weight loss in rodents [148][149][150]. Furthermore, the 5HT 2C receptor is related to the 5HT2A and 5HT2B receptors.…”

Section: 5ht 2c Receptor Agonistsmentioning

confidence: 98%

New Trends in Medicinal Chemistry Approaches to Antiobesity Therapy

Lee¹,

Song²,

Kang³

et al. 2009

CTMC

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The prevalences of overweightedness and obesity are increasing globally at frightening rates, driven by social and economic changes. Furthermore, obesity is associated with the pathogeneses of major diseases, particularly diabetes and cardiovascular diseases. However, no satisfactorily safe, effective obesity drugs are commercially available at the present time. Only two drugs have been approved in the United States for the long-term treatment of obesity, sibutramine and orlistat. However, these drugs are minimally effective and have significant side effects, which are likely inhibit their use. Therefore, there is a huge opportunity to make a significant impact on the lives of obese people through the discovery and development of additional pharmacotherapeutic options. In this review article, the authors focus on selected trends in medicinal chemistry and the approaches used to develop drugs for treating obesity.

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Local perfusion of mCPP into ventromedial hypothalamic nucleus, but not into lateral hypothalamic area and frontal cortex, inhibits food intake in rats

Cited by 21 publications

References 50 publications

Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake

Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake

5‐HT_2C antagonism blocks blood oxygen level‐dependent pharmacological‐challenge magnetic resonance imaging signal in rat brain areas related to feeding

New Trends in Medicinal Chemistry Approaches to Antiobesity Therapy

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Local perfusion of mCPP into ventromedial hypothalamic nucleus, but not into lateral hypothalamic area and frontal cortex, inhibits food intake in rats

Cited by 21 publications

References 50 publications

Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake

Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake

5‐HT2C antagonism blocks blood oxygen level‐dependent pharmacological‐challenge magnetic resonance imaging signal in rat brain areas related to feeding

New Trends in Medicinal Chemistry Approaches to Antiobesity Therapy

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5‐HT_2C antagonism blocks blood oxygen level‐dependent pharmacological‐challenge magnetic resonance imaging signal in rat brain areas related to feeding