Effects of the cannabinoid receptor antagonist SR 141716, alone and in combination with dexfenfluramine or naloxone, on food intake in rats

Rowland, Neil E.; Mukherjee, Monica; Robertson, Kimberly L.

doi:10.1007/s002130100910

Cited by 134 publications

(84 citation statements)

References 15 publications

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“…Whereas sibutramine, for example, advanced the BSS, thus indicating a satiating effect [355], the combination of sibutramine and the opioid antagonist naloxone showed rather infra-additive effects [355]. Combining fenfluramine with rimonabant had additive effects on food intake [356], whereas the combination of mCPP and naltrexone did not provide any support for a clinically useful combination [81]. In conclusion, these findings show that each potential combination requires individual testing.…”

Section: Serotonin and The Pharmacotherapy Of Obesitymentioning

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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Section: Serotonin and The Pharmacotherapy Of Obesitymentioning

confidence: 99%

Serotonin controlling feeding and satiety

Voigt

Fink

2015

Behavioural Brain Research

257

167

View full text Add to dashboard Cite

show abstract

“…72,73 In addition, food intake studies showed that rimonabant inhibited the intake of both regular chow or palatable food. 24,74,75 Tetrahydrocannabinol (THC) has also been shown to stimulate the intake of either chow or highfat sweetened diet. 76 These data generally support a model in which CB1R inverse agonists reduce the intake of all macronutrients with no selectivity related to palatability.…”

Section: Do Cb1r Agents Produce Weight Loss-independent Effects?mentioning

confidence: 99%

Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action and unanswered questions

Fong

Heymsfield

2009

Int J Obes

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Rimonabant and taranabant are two extensively studied cannabinoid-1 receptor (CB1R) inverse agonists. Their effects on in vivo peripheral tissue metabolism are generally well replicated. The central nervous system site of action of taranabant or rimonabant is firmly established based on brain receptor occupancy studies. At the whole-body level, the mechanism of action of CB1R inverse agonists includes a reduction in food intake and an increase in energy expenditure. At the tissue level, fat mass reduction, liver lipid reduction and improved insulin sensitivity have been shown. These effects on tissue metabolism are readily explained by CB1R inverse agonist acting on brain CB1R and indirectly influencing the tissue metabolism through the autonomic nervous system. It has also been hypothesized that rimonabant acts directly on adipocytes, hepatocytes, pancreatic islets or skeletal muscle in addition to acting on brain CB1R, although strong support for the contribution of peripherally located CB1R to in vivo efficacy is still lacking. This review will carefully examine the published literature and provide a perspective on what new tools and studies are required to address the peripheral site of action hypothesis.

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“…For example, a 1 mm 3 'hedonic hotspot' was recently found in the medial shell where m opioid receptor activation by DAMGO microinjections tripled positive 'liking' orofacial reactions that are elicited by sucrose taste in rats (Peciña and Berridge, 2005), and stimulated food intake (though the intake 'wanting' site extended further) (Bakshi and Kelley, 1993;Zhang and Kelley, 2000;Peciña and Berridge, 2005). Opioid and endocannabinoid neurotransmissions are known to positively interact (Tanda et al, 1997;Kirkham and Williams, 2001;Navarro et al, 2001;Rowland et al, 2001;Williams and Kirkham, 2002b;Verty et al, 2003;Solinas and Goldberg, 2005;Vigano et al, 2005;Caille and Parsons, 2006;Cota et al, 2006), raising the possibility that endocannabinoid receptor activation might increase 'liking' for natural rewards in the same hedonic hotspot of the medial accumbens shell where opioids do so.…”

Section: Introductionmentioning

confidence: 99%

Endocannabinoid Hedonic Hotspot for Sensory Pleasure: Anandamide in Nucleus Accumbens Shell Enhances ‘Liking’ of a Sweet Reward

Mahler

Smith

Berridge

2007

Neuropsychopharmacol

306

259

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Cannabinoid drugs such as D 9 -THC are euphoric and rewarding, and also stimulate food intake in humans and animals. Little is known about how naturally occurring endogenous brain cannabinoids mediate pleasure from food or other natural sensory rewards. The taste reactivity paradigm measures effects of brain manipulations on affective orofacial reactions to intraorally administered pleasant and unpleasant tastes. Here we tested if anandamide microinjection into medial nucleus accumbens shell enhances these affective reactions to sweet and bitter tastes in rats. Anandamide doubled the number of positive 'liking' reactions elicited by intraoral sucrose, without altering negative 'disliking' reactions to bitter quinine. Anandamide microinjections produced Fos plumes of approximately 0.02-1 mm 3 volume. Plume-based maps, integrated with behavioral data, identified the medial shell of accumbens as the anatomical hotspot responsible for hedonic amplification. Anandamide produced especially intense hedonic enhancement in a roughly 1.6 mm 3 'hedonic hotspot' in dorsal medial shell, where anandamide also stimulated eating behavior. These results demonstrate that endocannabinoid signals within medial accumbens shell specifically amplify the positive hedonic impact of a natural reward (though identification of the receptor specificity of this effect will require future studies). Identification of an endocannabinoid hotspot for sensory pleasure gives insight into brain mechanisms of natural reward, and may be relevant to understanding the neural effects of cannabinoid drugs of abuse and therapeutic agents.

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Effects of the cannabinoid receptor antagonist SR 141716, alone and in combination with dexfenfluramine or naloxone, on food intake in rats

Cited by 134 publications

References 15 publications

Serotonin controlling feeding and satiety

Serotonin controlling feeding and satiety

Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action and unanswered questions

Endocannabinoid Hedonic Hotspot for Sensory Pleasure: Anandamide in Nucleus Accumbens Shell Enhances ‘Liking’ of a Sweet Reward

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