Serotonin 2C receptor agonists and the behavioural satiety sequence in mice

Hewitt, Katherine N.; Lee, Michelle D.; Dourish, C T; Clifton, Peter G.

doi:10.1016/s0091-3057(01)00709-2

Cited by 114 publications

(99 citation statements)

References 31 publications

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“…5-HT 2C receptors and cocaine PJ Fletcher et al patterning of feeding-related behaviors (Hewitt et al, 2002). Overall, these data suggest that treatment with Ro60-0175 produces a blunted motivational state that results in reduced responding for drug and non-drug reinforcers.…”

Section: Discussionmentioning

confidence: 75%

“…In addition to reducing responding for cocaine, and to inhibiting reinstatement, Ro60-0175 reduces other behaviors including feeding (Hewitt et al, 2002) operant responding for food (Grottick et al, 2000) and for nicotine (Grottick et al, 2001). Therefore, it needs to be considered that this profile simply reflects a broad, non-specific impairment of behavior.…”

Section: Discussionmentioning

confidence: 99%

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The 5-HT2C Receptor Agonist Ro60-0175 Reduces Cocaine Self-Administration and Reinstatement Induced by the Stressor Yohimbine, and Contextual Cues

Fletcher

Rizos

Sinyard

et al. 2007

Neuropsychopharmacol

112

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Previously, we showed that the 5-HT 2C receptor agonist Ro60-0175 reduces cocaine self-administration, and the ability of cocaine to reinstate responding after extinction of drug-seeking behavior. The present experiments extended these findings further by determining whether the effects of Ro60-0175 on self-administration were sustained with repeated treatment, and whether Ro60-0175 altered reinstatement induced by the pharmacological stressor yohimbine, or by the context in which self-administration occurred. In Experiment 1, Ro60-0175 (1 mg/kg, s.c.) reduced cocaine (0.25 mg/infusion) self-administration maintained by a progressive ratio schedule. This reduction was sustained over eight daily injections. In Experiment 2, rats self-administered cocaine in daily 2 h sessions for 15 days on a FR1 schedule. Following extinction, yohimbine (1 mg/kg, i.p.) reinstated responding, and this effect was reduced dose dependently by Ro60-0175 (0.3-3 mg/kg, s.c.). In Experiment 3, rats were trained to respond for cocaine on a FR1 schedule in a distinct environmental context (A); responding was then extinguished in a different context (B). Reinstatement tests occurred in either context A or B.Responding was reinstated only when rats were tested in the original self-administration context (A). This reinstatement was reduced dose dependently by Ro60-0175. All effects of Ro60-0175 were blocked by the 5-HT 2C receptor antagonist SB242084. Thus, Ro60-0175, acting via 5-HT 2C receptors, reduces cocaine self-administration and cocaine-seeking triggered by a stressor and by drug-associated cues. The effects of Ro60-0175 do not exhibit tolerance within the 8-day test period. These results indicate that selective 5-HT 2C receptor agonists may be a useful pharmacological strategy for treatment of drug abuse.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

The 5-HT2C Receptor Agonist Ro60-0175 Reduces Cocaine Self-Administration and Reinstatement Induced by the Stressor Yohimbine, and Contextual Cues

Fletcher

Rizos

Sinyard

et al. 2007

Neuropsychopharmacol

112

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“…The model combines assessment of eating microstructural variables using the Sussex Ingestion Pattern Monitor (Yeomans 1996) alongside measures of emotional processing using the P1vital ® Oxford Emotional Test Battery (ETB) (Harmer et al 2004Murphy et al 2008). We examined the effect of a compound that has been reported to alter food intake and moodrelated behaviour in rodents, the preferential 5-HT2C receptor agonist metachlorophenylpiperazine (mCPP) (Kitchener and Dourish 1994;Kennett et al 1994;Hewitt et al 2002). The anorectic effects of mCPP in humans have been reported previously Sargent et al 1997) but detailed effects of this compound on appetite have yet to be 6 investigated.…”

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confidence: 99%

Effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine on appetite, food intake and emotional processing in healthy volunteers

et al. 2014

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(250 words)Rationale: The treatment of obesity is an increasing global health priority yet few effective drug treatments are currently available. The discovery of novel anti-obesity therapies could be assisted by the validation of experimental (translational) medicine models in healthy volunteers that assess efficacy and safety at an early stage of drug development. Objectives:To examine the effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) in an experimental medicine model assessing both appetite and mood. Methods: Using a between-subjects double blind placebo controlled design, 24 male and 24 female participants were randomly assigned to either placebo, 15mg or 30mg mCPP treatment groups. Lunch was eaten from a Universal Eating Monitor (UEM) that measured eating rate and participants completed the P1vital ® Oxford Emotional Test Battery (ETB) and a series of appetite and mood ratings. Results: mCPP reduced appetite, and in females, enhanced measures of satiation. The drug also enhanced memory for emotional material in the word recall and recognition memory tasks of the ETB. Conclusions: The results provide new insight into the effects of mCPP on appetite, satiety and memory in humans. In addition, our data provide an illustration of the value of measuring changes in appetite and mood in healthy volunteers to determine the potential efficacy and safety of novel anti-obesity drugs.

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“…Extracellular concentrations of serotonin and its metabolite 5-HIAA increase in rats' brains during spontaneous meals (44). The serotonin agonist fenfluramine, which both releases synaptic serotonin and blocks serotonin reuptake (14, 21), inhibits eating in rats by reducing meal size without affecting meal frequency or causing adverse behavioral effects (8,9,16,29,52). The most extensively studied serotonin receptor in relation to the control of eating is the serotonin 2C receptor (2CR) (51, 56).…”

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confidence: 99%

Loss of cholecystokinin and glucagon-like peptide-1-induced satiation in mice lacking serotonin 2C receptors

Asarian

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Asarian L. Loss of cholecystokinin and glucagon-like peptide-1-induced satiation in mice lacking serotonin 2C receptors. Am J Physiol Regul Integr Comp Physiol 296: R51-R56, 2009. First published November 12, 2008 doi:10.1152/ajpregu.90655.2008.-To investigate the role of serotonin 2C receptors (2CR), which are expressed only in the central nervous system, in the satiating actions of the gut peptides CCK and glucagon-like peptide 1 (GLP-1), we examined 1) the effect of null mutations of serotonin 2CR (2CR KO) on the eating-inhibitory potencies of dark-onset intraperitoneal injections of 0.9, 1.7, or 3.5 nmol/kg (1, 2, or 4 g/kg) CCK and 100, 200, and 400 nmol/kg (33, 66, or 132 g/kg) GLP-1, and 2) the effects of intraperitoneal injections of 1.7 nmol//kg CCK and 100 nmol/kg GLP-1 on neuronal activation in the brain, as measured by c-Fos expression. All CCK and GLP-1 doses decreased 30-min food intake in wild-type (WT) mice, but none of them did in 2CR KO mice. CCK increased the number of cells expressing c-Fos in the nucleus tractus solitarii (NTS) of WT, but not 2CR KO mice. CCK induced similar degrees of c-Fos expression in the paraventricular (PVN) and arcuate (Arc) nuclei of the hypothalamus of both genotypes. GLP-1, on the other hand, increased c-Fos expression similarly in the NTS of both genotypes and increased c-Fos expression more in the PVN and Arc of 2CR KO mice, but not WT mice. These results indicate that serotonin signaling via serotonin 2CR is necessary for the full satiating effects of CCK and GLP-1. In addition, they suggest that the satiating effects of the two peptides are mediated by different neural mechanisms. endocrine; eating; hormone; neural; immunocytochemistry; 5HT ON THE BASIS OF FULFILLMENT of criteria for endocrine satiation signals initially proposed by Gibbs et al. (20), intestinal CCK and GLP-1 are now considered to be physiological controls of eating (4,10,19,32). Both hormones are released during meals, and premeal administration of doses producing plasma hormone levels that are similar to prandial levels is sufficient to inhibit meal size in the absence of adverse effects in humans. Furthermore, administration of CCK 1 receptor antagonists in humans or rats, or GLP-1 receptor antagonists in rats, increases food intake (Williams D, personal communication); CCK 1 receptor antagonists also block the satiating effects of CCK secretagogues in humans and rats. Although the understanding of the roles of these peptides in physiology of eating has increased tremendously in the last two decades (19,39,41,54), the brain mechanisms underlying their effects are still unclear.Serotonin appears to be a key neurotransmitter in the central mediation of eating, including the control of meal size. Extracellular concentrations of serotonin and its metabolite 5-HIAA increase in rats' brains during spontaneous meals (44). The serotonin agonist fenfluramine, which both releases synaptic serotonin and blocks serotonin reuptake (14, 21), inhibits eating in rats by reducing meal size without affectin...

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Serotonin 2C receptor agonists and the behavioural satiety sequence in mice

Cited by 114 publications

References 31 publications

The 5-HT2C Receptor Agonist Ro60-0175 Reduces Cocaine Self-Administration and Reinstatement Induced by the Stressor Yohimbine, and Contextual Cues

The 5-HT2C Receptor Agonist Ro60-0175 Reduces Cocaine Self-Administration and Reinstatement Induced by the Stressor Yohimbine, and Contextual Cues

Effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine on appetite, food intake and emotional processing in healthy volunteers

Loss of cholecystokinin and glucagon-like peptide-1-induced satiation in mice lacking serotonin 2C receptors

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