Ghrelin increases intake of rewarding food in rodents

We investigated whether ghrelin action at the level of the ventral tegmental area (VTA), a key node in the mesolimbic reward system, is important for the rewarding and motivational aspects of the consumption of rewarding/palatable food. Mice with a disrupted gene encoding the ghrelin receptor (GHS-R1A) and rats treated peripherally with a GHS-R1A antagonist both show suppressed intake of rewarding food in a free choice (chow/rewarding food) paradigm. Moreover, accumbal dopamine release induced by rewarding food was absent in GHS-R1A knockout mice. Acute bilateral intra-VTA administration of ghrelin increased 1-hour consumption of rewarding food but not standard chow. In comparison with sham rats, VTA-lesioned rats had normal intracerebroventricular ghrelin-induced chow intake, although both intake of and time spent exploring rewarding food was decreased. Finally, the ability of rewarding food to condition a place preference was suppressed by the GHS-R1A antagonist in rats. Our data support the hypothesis that central ghrelin signaling at the level of the VTA is important for the incentive value of rewarding food

Suivi d'une cohorte de femmes fumeuses au sein d'une maternité de l'agglomération rouennaise

But : Évaluer le comportement des femmes fumeuses pendant leur grossesse et après l'accouchement, ainsi que l'information et le soutien qui leur sont apportés. Matériels et méthodes. Suivi du statut tabagique de 160 femmes fumeuses en début de grossesse, recrutées dans une maternité de niveau Il a, qui ont ensuite répondu à un questionnaire téléphonique quatre mois après leur accouchement. Résultats. Vingt cinq pour cent des femmes enceintes étaient fumeuses. Cinquante neuf pour cent d'entre-elles fument encore au troisième trimestre de la grossesse. Parmi les femmes enceintes fumeuses qui ont arrêté au cours de la grossesse, 41% rechutent après l'accouchement. Les motifs de rechute fréquemment évoqués sont l'arrêt de l'allaitement, le tabagisme environnemental et le stress. Lors de la reprise, la consommation est deux fois moins importante qu'avant la grossesse. Le conjoint fumeur influence négativement la réussite du sevrage. Le bébé d'une mère qui fume a moins de chance d'être allaité, et s'il est allaité, il a plus de risque d'être sevré précocement. Le poids de naissance des bébés de mères fumeuses est inférieur à celui des mères non-fumeuses (178g). Même si les femmes sont informées de l'existence d'une consultation d'aide au sevrage tabagique, le taux de participation reste faible.Conclusion. La prise en charge de la femme enceinte fumeuse et de son conjoint doit être au centre des préoccupations des pouvoirs publics. Tous les acteurs de santé qui rencontrent des femmes enceintes doivent être impliqués. Ils doivent être formés à l'information systématique, à la mesure du CO expiré en consultation et à la prescription des traitements substitutifs. Les consultations d'aide au sevrage tabagique par des tabacologues doivent se multiplier notamment dans les maternités. La prise en charge après la naissance ne doit pas être oubliée.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Morphine 6-Glucuronide and Morphine 3-Glucuronide As Molecular Chameleons with Unexpected Lipophilicity

Morphine 6-glucuronide, but not morphine 3-glucuronide, is a highly potent opiate receptor agonist. In fact, there is converging evidence that much of the analgesic effect occurring after morphine treatment in humans is due to this metabolite rather than to the parent drug. Yet glucuronides as a rule are considered as highly polar metabolites unable to cross the blood-brain barrier and rapidly excreted by the urinary and/or biliary routes. Here, we report that morphine 6-glucuronide, and to a lesser extent morphine 3-glucuronide, are far more lipophilic than predicted, and in fact not much less lipophilic than morphine itself. Force-field and quantum mechanical calculations indicate that the two glucuronides can exist in conformational equilibrium between extended and folded forms. The extended conformers, because they efficiently expose their polar groups, must be highly hydrophilic forms predominating in polar media such as water; in contrast, the folded conformers mask part of their polar groups, thus being more lipophilic and likely to predominate in media of low polarity such as biological membrane

Ghrelin control of GH secretion and feeding behaviour: the role of the GHS-R1a receptor studied in vivo and in vitro using novel non-peptide ligands

Journal Article Research Support, Non-U.S. Gov't Italy EwdEnergy homeostasis is controlled by a complex regulatory system of molecules that affect food intake and that are critical for maintaining a stable body weight during life. Ghrelin is a peptide of 28 amino acid synthesized predominantly by the stomach and the gut, which activate the type 1a growth hormone (GH) secretagogue receptor (GHS-R1a), a G-protein coupled receptor. The acylated form of ghrelin potently stimulates GH secretion both in vitro and in vivo in several animal species, including humans. Beside the endocrine effect, ghrelin shows also extraendocrine activities, including stimulation of feeding behaviour. Several classes of small synthetic peptide and non-peptide ligands of the GHS-R1a have been described and are able to release GH and stimulate food intake. However, in time, it appeared that the stimulating effects on GH secretion could be divorced from those on food intake, suggesting that more than a single receptor might be involved. Several experimental data have even questioned the physiological role of ghrelin in the control of GH secretion and energy metabolism. By using novel agonists, partial agonists, and antagonists for the GHS-R1a receptor, we have studied whether the stimulation of this receptor could account for the purported physiological role of ghrelin. Our results demonstrate that the ability to bind in vitro the GHS-R1a is not predictive of the in vivo biological activity of the compounds and that the endocrine and extraendocrine effects could be mediated also by receptors different from the GHS-R1a

Ghrelin control of GH secretion and feeding behaviour: the role of the GHS-R1a receptor studied in vivo and in vitro using novel non-peptide ligands

Journal Article Research Support, Non-U.S. Gov't Italy EwdEnergy homeostasis is controlled by a complex regulatory system of molecules that affect food intake and that are critical for maintaining a stable body weight during life. Ghrelin is a peptide of 28 amino acid synthesized predominantly by the stomach and the gut, which activate the type 1a growth hormone (GH) secretagogue receptor (GHS-R1a), a G-protein coupled receptor. The acylated form of ghrelin potently stimulates GH secretion both in vitro and in vivo in several animal species, including humans. Beside the endocrine effect, ghrelin shows also extraendocrine activities, including stimulation of feeding behaviour. Several classes of small synthetic peptide and non-peptide ligands of the GHS-R1a have been described and are able to release GH and stimulate food intake. However, in time, it appeared that the stimulating effects on GH secretion could be divorced from those on food intake, suggesting that more than a single receptor might be involved. Several experimental data have even questioned the physiological role of ghrelin in the control of GH secretion and energy metabolism. By using novel agonists, partial agonists, and antagonists for the GHS-R1a receptor, we have studied whether the stimulation of this receptor could account for the purported physiological role of ghrelin. Our results demonstrate that the ability to bind in vitro the GHS-R1a is not predictive of the in vivo biological activity of the compounds and that the endocrine and extraendocrine effects could be mediated also by receptors different from the GHS-R1a