Activity-Based Anorexia Dynamically Dysregulates the Glutamatergic Synapse in the Nucleus Accumbens of Female Adolescent Rats
Intense physical activity and dieting are core symptoms of anorexia nervosa (AN). Their combination evolves into compulsivity, leading the patient into an out-of-control spiral. AN patients exhibit an altered activation of nucleus accumbens (NAc), revealing a dysfunctional mesocorticolimbic reward c...
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MDPI AG
2020-11-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/12/12/3661 |
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| author | Francesca Mottarlini Giorgia Bottan Benedetta Tarenzi Alessandra Colciago Fabio Fumagalli Lucia Caffino |
| author_facet | Francesca Mottarlini Giorgia Bottan Benedetta Tarenzi Alessandra Colciago Fabio Fumagalli Lucia Caffino |
| author_sort | Francesca Mottarlini |
| collection | DOAJ |
| description | Intense physical activity and dieting are core symptoms of anorexia nervosa (AN). Their combination evolves into compulsivity, leading the patient into an out-of-control spiral. AN patients exhibit an altered activation of nucleus accumbens (NAc), revealing a dysfunctional mesocorticolimbic reward circuitry in AN. Since evidence exists that a dysregulation of the glutamate system in the NAc influences reward and taking advantage of the activity-based anorexia (ABA) rat model, which closely mimics the hallmarks of AN, we investigated the involvement of the glutamatergic signaling in the NAc in this experimental model. We here demonstrate that food restriction causes hyperactive and compulsive behavior in rodents, inducing an escalation of physical activity, which results in dramatic weight loss. Analysis of the glutamate system revealed that, in the acute phase of the pathology, ABA rats increased the membrane expression of GluA1 AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor subunits together with its scaffolding protein SAP97. Recovery of body weight reduced GluN2A/2B balance together with the expression of their specific scaffolding proteins, thus suggesting persistent maladaptive neurotransmission. Taken together, AMPA and NMDA (N-methyl-D-aspartate) receptor subunit reorganization may play a role in the motivational mechanisms underlying AN. |
| first_indexed | 2024-03-10T14:29:15Z |
| format | Article |
| id | doaj.art-882e608d81dc461bacc1412918018134 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T14:29:15Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-882e608d81dc461bacc14129180181342023-11-20T22:42:16ZengMDPI AGNutrients2072-66432020-11-011212366110.3390/nu12123661Activity-Based Anorexia Dynamically Dysregulates the Glutamatergic Synapse in the Nucleus Accumbens of Female Adolescent RatsFrancesca Mottarlini0Giorgia Bottan1Benedetta Tarenzi2Alessandra Colciago3Fabio Fumagalli4Lucia Caffino5Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, ItalyIntense physical activity and dieting are core symptoms of anorexia nervosa (AN). Their combination evolves into compulsivity, leading the patient into an out-of-control spiral. AN patients exhibit an altered activation of nucleus accumbens (NAc), revealing a dysfunctional mesocorticolimbic reward circuitry in AN. Since evidence exists that a dysregulation of the glutamate system in the NAc influences reward and taking advantage of the activity-based anorexia (ABA) rat model, which closely mimics the hallmarks of AN, we investigated the involvement of the glutamatergic signaling in the NAc in this experimental model. We here demonstrate that food restriction causes hyperactive and compulsive behavior in rodents, inducing an escalation of physical activity, which results in dramatic weight loss. Analysis of the glutamate system revealed that, in the acute phase of the pathology, ABA rats increased the membrane expression of GluA1 AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor subunits together with its scaffolding protein SAP97. Recovery of body weight reduced GluN2A/2B balance together with the expression of their specific scaffolding proteins, thus suggesting persistent maladaptive neurotransmission. Taken together, AMPA and NMDA (N-methyl-D-aspartate) receptor subunit reorganization may play a role in the motivational mechanisms underlying AN.https://www.mdpi.com/2072-6643/12/12/3661nucleus accumbensreward circuitglutamatergic receptorsactivity-based anorexiaadolescencefemale rats |
| spellingShingle | Francesca Mottarlini Giorgia Bottan Benedetta Tarenzi Alessandra Colciago Fabio Fumagalli Lucia Caffino Activity-Based Anorexia Dynamically Dysregulates the Glutamatergic Synapse in the Nucleus Accumbens of Female Adolescent Rats Nutrients nucleus accumbens reward circuit glutamatergic receptors activity-based anorexia adolescence female rats |
| title | Activity-Based Anorexia Dynamically Dysregulates the Glutamatergic Synapse in the Nucleus Accumbens of Female Adolescent Rats |
| title_full | Activity-Based Anorexia Dynamically Dysregulates the Glutamatergic Synapse in the Nucleus Accumbens of Female Adolescent Rats |
| title_fullStr | Activity-Based Anorexia Dynamically Dysregulates the Glutamatergic Synapse in the Nucleus Accumbens of Female Adolescent Rats |
| title_full_unstemmed | Activity-Based Anorexia Dynamically Dysregulates the Glutamatergic Synapse in the Nucleus Accumbens of Female Adolescent Rats |
| title_short | Activity-Based Anorexia Dynamically Dysregulates the Glutamatergic Synapse in the Nucleus Accumbens of Female Adolescent Rats |
| title_sort | activity based anorexia dynamically dysregulates the glutamatergic synapse in the nucleus accumbens of female adolescent rats |
| topic | nucleus accumbens reward circuit glutamatergic receptors activity-based anorexia adolescence female rats |
| url | https://www.mdpi.com/2072-6643/12/12/3661 |
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