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Anorexia induced by activation of serotonin 5-HT 4 receptors is mediated by increases in CART in the nucleus accumbens
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| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
|---|---|
| Personen und Körperschaften: | , , , , , , , , |
| In: | Proceedings of the National Academy of Sciences, 104, 2007, 41, S. 16335-16340 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
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| Schlagwörter: |
| author_facet |
Jean, Alexandra Conductier, Grégory Manrique, Christine Bouras, Constantin Berta, Philippe Hen, René Charnay, Yves Bockaert, Joël Compan, Valérie Jean, Alexandra Conductier, Grégory Manrique, Christine Bouras, Constantin Berta, Philippe Hen, René Charnay, Yves Bockaert, Joël Compan, Valérie |
|---|---|
| author |
Jean, Alexandra Conductier, Grégory Manrique, Christine Bouras, Constantin Berta, Philippe Hen, René Charnay, Yves Bockaert, Joël Compan, Valérie |
| spellingShingle |
Jean, Alexandra Conductier, Grégory Manrique, Christine Bouras, Constantin Berta, Philippe Hen, René Charnay, Yves Bockaert, Joël Compan, Valérie Proceedings of the National Academy of Sciences Anorexia induced by activation of serotonin 5-HT 4 receptors is mediated by increases in CART in the nucleus accumbens Multidisciplinary |
| author_sort |
jean, alexandra |
| spelling |
Jean, Alexandra Conductier, Grégory Manrique, Christine Bouras, Constantin Berta, Philippe Hen, René Charnay, Yves Bockaert, Joël Compan, Valérie 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.0701471104 <jats:p> Anorexia nervosa is a growing concern in mental health, often inducing death. The potential neuronal deficits that may underlie abnormal inhibitions of food intake, however, remain largely unexplored. We hypothesized that anorexia may involve altered signaling events within the nucleus accumbens (NAc), a brain structure involved in reward. We show here that direct stimulation of serotonin (5-hydroxytryptamine, 5-HT) 4 receptors (5-HT <jats:sub>4</jats:sub> R) in the NAc reduces the physiological drive to eat and increases CART (cocaine- and amphetamine-regulated transcript) mRNA levels in fed and food-deprived mice. It further shows that injecting 5-HT <jats:sub>4</jats:sub> R antagonist or siRNA-mediated 5-HT <jats:sub>4</jats:sub> R knockdown into the NAc induced hyperphagia only in fed mice. This hyperphagia was not associated with changes in CART mRNA expression in the NAc in fed and food-deprived mice. Results include that 5-HT <jats:sub>4</jats:sub> R control CART mRNA expression into the NAc via a cAMP/PKA signaling pathway. Considering that CART may interfere with food- and drug-related rewards, we tested whether the appetite suppressant properties of 3,4- <jats:italic>N</jats:italic> -methylenedioxymethamphetamine (MDMA, ecstasy) involve the 5-HT <jats:sub>4</jats:sub> R. Using 5-HT <jats:sub>4</jats:sub> R knockout mice, we demonstrate that 5-HT <jats:sub>4</jats:sub> R are required for the anorectic effect of MDMA as well as for the MDMA-induced enhancement of CART mRNA expression in the NAc. Directly injecting CART peptide or CART siRNA into the NAc reduces or increases food consumption, respectively. Finally, stimulating 5-HT <jats:sub>4</jats:sub> R- and MDMA-induced anorexia were both reduced by injecting CART siRNA into the NAc. Collectively, these results demonstrate that 5-HT <jats:sub>4</jats:sub> R-mediated up-regulation of CART in the NAc triggers the appetite-suppressant effects of ecstasy. </jats:p> Anorexia induced by activation of serotonin 5-HT <sub>4</sub> receptors is mediated by increases in CART in the nucleus accumbens Proceedings of the National Academy of Sciences |
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| title |
Anorexia induced by activation of serotonin 5-HT 4 receptors is mediated by increases in CART in the nucleus accumbens |
| title_unstemmed |
Anorexia induced by activation of serotonin 5-HT 4 receptors is mediated by increases in CART in the nucleus accumbens |
| title_full |
Anorexia induced by activation of serotonin 5-HT 4 receptors is mediated by increases in CART in the nucleus accumbens |
| title_fullStr |
Anorexia induced by activation of serotonin 5-HT 4 receptors is mediated by increases in CART in the nucleus accumbens |
| title_full_unstemmed |
Anorexia induced by activation of serotonin 5-HT 4 receptors is mediated by increases in CART in the nucleus accumbens |
| title_short |
Anorexia induced by activation of serotonin 5-HT 4 receptors is mediated by increases in CART in the nucleus accumbens |
| title_sort |
anorexia induced by activation of serotonin 5-ht
<sub>4</sub>
receptors is mediated by increases in cart in the nucleus accumbens |
| topic |
Multidisciplinary |
| url |
http://dx.doi.org/10.1073/pnas.0701471104 |
| publishDate |
2007 |
| physical |
16335-16340 |
| description |
<jats:p>
Anorexia nervosa is a growing concern in mental health, often inducing death. The potential neuronal deficits that may underlie abnormal inhibitions of food intake, however, remain largely unexplored. We hypothesized that anorexia may involve altered signaling events within the nucleus accumbens (NAc), a brain structure involved in reward. We show here that direct stimulation of serotonin (5-hydroxytryptamine, 5-HT) 4 receptors (5-HT
<jats:sub>4</jats:sub>
R) in the NAc reduces the physiological drive to eat and increases CART (cocaine- and amphetamine-regulated transcript) mRNA levels in fed and food-deprived mice. It further shows that injecting 5-HT
<jats:sub>4</jats:sub>
R antagonist or siRNA-mediated 5-HT
<jats:sub>4</jats:sub>
R knockdown into the NAc induced hyperphagia only in fed mice. This hyperphagia was not associated with changes in CART mRNA expression in the NAc in fed and food-deprived mice. Results include that 5-HT
<jats:sub>4</jats:sub>
R control CART mRNA expression into the NAc via a cAMP/PKA signaling pathway. Considering that CART may interfere with food- and drug-related rewards, we tested whether the appetite suppressant properties of 3,4-
<jats:italic>N</jats:italic>
-methylenedioxymethamphetamine (MDMA, ecstasy) involve the 5-HT
<jats:sub>4</jats:sub>
R. Using 5-HT
<jats:sub>4</jats:sub>
R knockout mice, we demonstrate that 5-HT
<jats:sub>4</jats:sub>
R are required for the anorectic effect of MDMA as well as for the MDMA-induced enhancement of CART mRNA expression in the NAc. Directly injecting CART peptide or CART siRNA into the NAc reduces or increases food consumption, respectively. Finally, stimulating 5-HT
<jats:sub>4</jats:sub>
R- and MDMA-induced anorexia were both reduced by injecting CART siRNA into the NAc. Collectively, these results demonstrate that 5-HT
<jats:sub>4</jats:sub>
R-mediated up-regulation of CART in the NAc triggers the appetite-suppressant effects of ecstasy.
</jats:p> |
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| author | Jean, Alexandra, Conductier, Grégory, Manrique, Christine, Bouras, Constantin, Berta, Philippe, Hen, René, Charnay, Yves, Bockaert, Joël, Compan, Valérie |
| author_facet | Jean, Alexandra, Conductier, Grégory, Manrique, Christine, Bouras, Constantin, Berta, Philippe, Hen, René, Charnay, Yves, Bockaert, Joël, Compan, Valérie, Jean, Alexandra, Conductier, Grégory, Manrique, Christine, Bouras, Constantin, Berta, Philippe, Hen, René, Charnay, Yves, Bockaert, Joël, Compan, Valérie |
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| description | <jats:p> Anorexia nervosa is a growing concern in mental health, often inducing death. The potential neuronal deficits that may underlie abnormal inhibitions of food intake, however, remain largely unexplored. We hypothesized that anorexia may involve altered signaling events within the nucleus accumbens (NAc), a brain structure involved in reward. We show here that direct stimulation of serotonin (5-hydroxytryptamine, 5-HT) 4 receptors (5-HT <jats:sub>4</jats:sub> R) in the NAc reduces the physiological drive to eat and increases CART (cocaine- and amphetamine-regulated transcript) mRNA levels in fed and food-deprived mice. It further shows that injecting 5-HT <jats:sub>4</jats:sub> R antagonist or siRNA-mediated 5-HT <jats:sub>4</jats:sub> R knockdown into the NAc induced hyperphagia only in fed mice. This hyperphagia was not associated with changes in CART mRNA expression in the NAc in fed and food-deprived mice. Results include that 5-HT <jats:sub>4</jats:sub> R control CART mRNA expression into the NAc via a cAMP/PKA signaling pathway. Considering that CART may interfere with food- and drug-related rewards, we tested whether the appetite suppressant properties of 3,4- <jats:italic>N</jats:italic> -methylenedioxymethamphetamine (MDMA, ecstasy) involve the 5-HT <jats:sub>4</jats:sub> R. Using 5-HT <jats:sub>4</jats:sub> R knockout mice, we demonstrate that 5-HT <jats:sub>4</jats:sub> R are required for the anorectic effect of MDMA as well as for the MDMA-induced enhancement of CART mRNA expression in the NAc. Directly injecting CART peptide or CART siRNA into the NAc reduces or increases food consumption, respectively. Finally, stimulating 5-HT <jats:sub>4</jats:sub> R- and MDMA-induced anorexia were both reduced by injecting CART siRNA into the NAc. Collectively, these results demonstrate that 5-HT <jats:sub>4</jats:sub> R-mediated up-regulation of CART in the NAc triggers the appetite-suppressant effects of ecstasy. </jats:p> |
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| spelling | Jean, Alexandra Conductier, Grégory Manrique, Christine Bouras, Constantin Berta, Philippe Hen, René Charnay, Yves Bockaert, Joël Compan, Valérie 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.0701471104 <jats:p> Anorexia nervosa is a growing concern in mental health, often inducing death. The potential neuronal deficits that may underlie abnormal inhibitions of food intake, however, remain largely unexplored. We hypothesized that anorexia may involve altered signaling events within the nucleus accumbens (NAc), a brain structure involved in reward. We show here that direct stimulation of serotonin (5-hydroxytryptamine, 5-HT) 4 receptors (5-HT <jats:sub>4</jats:sub> R) in the NAc reduces the physiological drive to eat and increases CART (cocaine- and amphetamine-regulated transcript) mRNA levels in fed and food-deprived mice. It further shows that injecting 5-HT <jats:sub>4</jats:sub> R antagonist or siRNA-mediated 5-HT <jats:sub>4</jats:sub> R knockdown into the NAc induced hyperphagia only in fed mice. This hyperphagia was not associated with changes in CART mRNA expression in the NAc in fed and food-deprived mice. Results include that 5-HT <jats:sub>4</jats:sub> R control CART mRNA expression into the NAc via a cAMP/PKA signaling pathway. Considering that CART may interfere with food- and drug-related rewards, we tested whether the appetite suppressant properties of 3,4- <jats:italic>N</jats:italic> -methylenedioxymethamphetamine (MDMA, ecstasy) involve the 5-HT <jats:sub>4</jats:sub> R. Using 5-HT <jats:sub>4</jats:sub> R knockout mice, we demonstrate that 5-HT <jats:sub>4</jats:sub> R are required for the anorectic effect of MDMA as well as for the MDMA-induced enhancement of CART mRNA expression in the NAc. Directly injecting CART peptide or CART siRNA into the NAc reduces or increases food consumption, respectively. Finally, stimulating 5-HT <jats:sub>4</jats:sub> R- and MDMA-induced anorexia were both reduced by injecting CART siRNA into the NAc. Collectively, these results demonstrate that 5-HT <jats:sub>4</jats:sub> R-mediated up-regulation of CART in the NAc triggers the appetite-suppressant effects of ecstasy. </jats:p> Anorexia induced by activation of serotonin 5-HT <sub>4</sub> receptors is mediated by increases in CART in the nucleus accumbens Proceedings of the National Academy of Sciences |
| spellingShingle | Jean, Alexandra, Conductier, Grégory, Manrique, Christine, Bouras, Constantin, Berta, Philippe, Hen, René, Charnay, Yves, Bockaert, Joël, Compan, Valérie, Proceedings of the National Academy of Sciences, Anorexia induced by activation of serotonin 5-HT 4 receptors is mediated by increases in CART in the nucleus accumbens, Multidisciplinary |
| title | Anorexia induced by activation of serotonin 5-HT 4 receptors is mediated by increases in CART in the nucleus accumbens |
| title_full | Anorexia induced by activation of serotonin 5-HT 4 receptors is mediated by increases in CART in the nucleus accumbens |
| title_fullStr | Anorexia induced by activation of serotonin 5-HT 4 receptors is mediated by increases in CART in the nucleus accumbens |
| title_full_unstemmed | Anorexia induced by activation of serotonin 5-HT 4 receptors is mediated by increases in CART in the nucleus accumbens |
| title_short | Anorexia induced by activation of serotonin 5-HT 4 receptors is mediated by increases in CART in the nucleus accumbens |
| title_sort | anorexia induced by activation of serotonin 5-ht <sub>4</sub> receptors is mediated by increases in cart in the nucleus accumbens |
| title_unstemmed | Anorexia induced by activation of serotonin 5-HT 4 receptors is mediated by increases in CART in the nucleus accumbens |
| topic | Multidisciplinary |
| url | http://dx.doi.org/10.1073/pnas.0701471104 |