Hypothalamic Neurochemistry and Feeding Behavioral Responses to Clonidine, an Alpha-2-Agonist, and to Trifluoromethylphenylpiperazine, a Putative 5-Hydroxytryptamine-1B Agonist, in Genetically Obese Zucker Rats

Koulu, Markku; Huupponen, Risto; Hänninen, Ham; Pesonen, Ullamari; Rouru, Juha; Seppαlä, Timo

doi:10.1159/000125635

Cited by 27 publications

(3 citation statements)

References 31 publications

(54 reference statements)

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“…However, one difference between normal and diabetic NTS slices by the evoked stimulated release became apparent when the cb-adrenergic ef fects of clonidine were examined in the [3H]NE-loaded NTS slices. In the present study and consistent with previous observa tions [36,41], clonidine reduced the [3H]NE release in both normal and diabetic slices by significantly reducing S2 fractional release, presumably through ob-adrenoceptor stimula tion. However, diabetic tissue slices as a group were not depressed as much as normal animal slices; there was a significant differ ence between the two clonidine-perfused groups (p< 0.05).…”

Section: Discussionsupporting

confidence: 93%

Effect of Insulin and Clonidine on the Evoked Release of Norepinephrine and Serotonin from the Nucleus tractus solitarius of the Diabetic Rat

Dunbar

Clough-Helfman²,

Barraco³

et al. 1995

Pharmacology

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Dorsal medullary brain slices containing primarily the nucleus tractus solitarius (NTS) were obtained from normal or 40- to 50-day streptozotocin-diabetic rats and employed for superfusion studies of evoked transmitter release. Electrically stimulated (25 mA, 2-ms pulses, 3 Hz, 1 min) release of [³H]norepinephrine ([³H]NE) or [³H]5-hydroxytryptamine ([³H]5-HT) from 400-µm NTS slices stimulated at 75 min (S₁) and 130 min (S₂) resulted in S₂/S₁ release ratios that were not different between normal controls or diabetic control groups. Perfusion of normal [³H]NE-loaded slices with 0.1 µmol/l clonidine reduced the S₂/S₁ ratio by 23% (p < 0.05) which was uniform in the caudal, subpostremal, and intermediate segment levels of the NTS. In diabetic NTS slices, the S₂/S₁ ratio was significantly less reduced by clonidine in both the subpostremal (–3%) and intermediate (–11%) slice regions. Blockade of α₂-adrenoceptors with yohimbine (0.1 µmol/l) enhanced (p < 0.05) [³H]NE release (S₂/S1 ratios) in slices from both normal and diabetic rats. Perfusion of [³H]NE-loaded slices with 5 mU/ml insulin did not affect S₂ release. Evoked S₂/S₁ release ratios from NTS slices loaded with [³H]5-HT did not differ between normal control and diabetic control groups. Clonidine (0.1 µmol/l) reduced S₂-evoked release in both normal (–30%) and diabetic (–44%) slices, but the groups were not different from each other. Superfusion with 5 mU/ml insulin did not alter S₂/S₁ ratios in normal [³H]5-HT loaded slices, but did increase the diabetic NTS slice S₂/S₁ ratio to 1.40 ± 0.06 (p < 0.01). In summary, it appears that α₂-adrenoceptor-mediated inhibition of [³H]NE release in the NTS was selectively attenuated in a regionally specific manner in diabetic animals. Release inhibition may be associated with receptor downregulation in NTS regions associated with cardiovascular reflex transmission. Insulin superfusion augmented [³H]5-HT release in the diabetic NTS slices, possibly through increased transmitter synthesis or improved synaptic release.

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Section: Discussionsupporting

confidence: 93%

Effect of Insulin and Clonidine on the Evoked Release of Norepinephrine and Serotonin from the Nucleus tractus solitarius of the Diabetic Rat

Dunbar

Clough-Helfman²,

Barraco³

et al. 1995

Pharmacology

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“…Considering these changes in brain 5-HT metabolism it appears somewhat surprising though that the hypophagic effects of fenfluramine, the SSRI fluoxetine, and the 5-HT1B/2C agonist TFMPP and 5-HT2A/2C agonists were similar in lean and obese Zucker rats [318][319][320][321][322].…”

Section: Changes In the Brain Satiety In Different Nutritional Statesmentioning

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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“…Altered noradrenergic neurotransmission has also been associated with obesity and abnormalities in food intake. Norepinephrine injected into the PVN stimulates food intake (18), and obese Zucker rats show an enhanced feeding response to peripheral administration of the a2 agonist, clonidine (17). Moreover, binding of the a 1 antagonist, prazosin, is higher in the dorsomedial hypothalamic nucleus, amygdala, and somatosensory cortex of obese vs. lean (FdFu) Zucker rats as is the VMN ap-al-adrenoreceptor ratio (21).…”

Section: Introductionmentioning

confidence: 99%

Hypothalamic Monoaminergic Activity in 11‐Week‐Old Cold‐Exposed Female Lean (Fa/Fa) and Obese (fa/fa) Zucker Rats

Routh

Horwitz

Gietzen³

et al. 1994

Obesity Research

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We previously reported that serotonergic activity was reduced in the ventromedial hypothalamic nucleus (VMN) of obese vs. lean male Zucker rats. To verify that this reduction was associated with genotype rather than gender, we measured monoamines and their major metabolites in hypothalamic nuclei of 11-week-old female lean (Fa/Fa) and obese (fa/fa) Zucker rats. In addition, since the thermic response to cold is reported to differ between lean and obese rats, some rats were also exposed to 9 degrees or 22 degrees C for 2h to determine if cold exposure altered hypothalamic monoaminergic activity. As in males, levels of 5-hydroxyindoleacetic acid [5-HIAA; major metabolite of serotonin (5-HT)] and the ratio of 5-HIAA/5-HT were lower in the VMN of obese vs. lean females (P = 0.008, 0.001, respectively). 5-HIAA/5-HT was also reduced in the paraventricular (PVN) and suprachiasmatic nuclei (SCN) of the obese compared to the lean females. Cold exposure significantly stimulated brown fat mitochondrial GDP binding in lean but not obese rats. Similarly, levels of norepinephrine, dopamine (DA), 5-HIAA, and 5-HT in the PVN, and 5-HIAA in the SCN increased in cold-exposed lean but not obese rats. In contrast, VMN and preoptic 3,4-dihydroxyphenylacetic acid (DOPAC; major metabolite of DA) increased in the cold-exposed obese but not lean animals. We conclude that: (1) the blunted peripheral response to cold in obese vs. lean Zucker rats is accompanied by altered hypothalamic monoaminergic activity, the physiological role of which needs further evaluation; and 2) depressed VMN serotonergic activity is associated with the obese genotype (fa/fa) rather than gender and as such may contribute to the reduced sympathetic and enhanced parasympathetic outflow from the VMN.

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Hypothalamic Neurochemistry and Feeding Behavioral Responses to Clonidine, an Alpha-2-Agonist, and to Trifluoromethylphenylpiperazine, a Putative 5-Hydroxytryptamine-1B Agonist, in Genetically Obese Zucker Rats

Cited by 27 publications

References 31 publications

Effect of Insulin and Clonidine on the Evoked Release of Norepinephrine and Serotonin from the Nucleus tractus solitarius of the Diabetic Rat

Effect of Insulin and Clonidine on the Evoked Release of Norepinephrine and Serotonin from the Nucleus tractus solitarius of the Diabetic Rat

Serotonin controlling feeding and satiety

Hypothalamic Monoaminergic Activity in 11‐Week‐Old Cold‐Exposed Female Lean (Fa/Fa) and Obese (fa/fa) Zucker Rats

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