Adolescent Nicotine Exposure Induces Molecular and Neuronal Features of Depressive Disorder in Adulthood in the Mesolimbic Dopamine System
Notice bibliographique
Résumé
Introduction/Objectives Smoking tobacco is the leading cause of preventable death world‐wide and the main psychoactive component of tobacco, nicotine, is associated with short‐ and long‐term mood‐state alterations. Adolescent nicotine exposure has been shown to induce long‐term depressive and anxiety‐related symptoms in adulthood. Nicotine exposure increases ventral tegmental area (VTA) dopaminergic (DA) inputs to the nucleus accumbens shell (NAcSh), comprising the mesolimbic DA system. Disturbances in the mesolimbic system are well‐established neuropathological correlates of mood disorders, however, the mechanisms by which adolescent nicotine exposure may cause the later development of mood and anxiety disorders is not currently understood. Mood disorders precipitate changes in activation state of intra‐cellular targets, such as glycogen synthase‐3 (GSK3) and extracellular signal‐regulated kinase (ERK). The objectives of the present study are to examine the effects of adolescent nicotine exposure on later adulthood neurobiological phenotypes associated with mood disorders. Methods Adolescent male Sprague‐Dawley rats were either administered 0.4mg/kg nicotine or saline vehicle injections three times per day for 11 days during a critical period of rodent adolescent neurodevelopment (post‐natal day 35–45). Rats matured into early adulthood (post‐natal day 65) and the VTA and NAc were subjected to protein extraction to examine intracellular molecular protein expression and activation profiles. Separate vehicle and nicotine‐treated groups underwent electrophysiology to record VTA and NAcSh neuronal activity. The VTA and NAcSh DA and medium spiny neuron (MSN) activity was recorded in vehicle and nicotine treated groups using dual‐cell neuronal recordings. Baseline recordings were examined along with recordings following a 0.4mg/kg nicotine injection and a subthreshold dose of 0.1mg/kg. Results Consistent with phenotypes observed in human depression, molecular analyses of the NAc revealed significant increases in the phosphorylation states of ERK1/2 (1: p=0.0219, 2: p=0.0151), GSK3 phosphorylation state (1: p=0.0029, 2: p=0.0028), and pGSK3:tGSK3 (site1: p=0.0165, site2: p=0.0291) in nicotine vs. vehicle treated rats. Furthermore, consistent with dysregulated mesolimbic activity states present in mood disorders, preliminary electrophysiological results indicate a larger increase in VTA DA and NAcSh MSN cellular firing frequency and burst rate in the nicotine treated group compared to the control group when subjected to 0.4mg/kg and o.1mg/kg doses of nicotine in adulthood. Conclusion Our results indicate that nicotine exposure in adolescence elicits long‐term changes in neuronal activity and intracellular molecular activation states, consistent with phenotypes observed in clinical mood disorder populations. Together, these findings identify a novel molecular and neuronal mechanism directly in the mesolimbic DA system, underlying the effects of adolescent nicotine exposure on the later development of mood disorders in adulthood. Support or Funding Information This work was supported by the Canadian Institutes of Health Research (MOP‐123378). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».