Transient Nicotine Exposure in Early Adolescent Male Mice Freezes Their Dopamine Circuits in an Immature State

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Oct 18

PMID 39424848

Authors

Lauren M Reynolds

Aylin Gulmez

Sophie L Fayad

Renan Costa Campos

Daiana Rigoni

Claire Nguyen

Tinaig Le Borgne

Thomas Topilko

Domitille Rajot

Clara Franco

Sebastian P Fernandez

Fabio Marti

Nicolas Heck

Alexandre Mourot

Nicolas Renier

Jacques Barik

Philippe Faure

Affiliations

Soon will be listed here.

Abstract

How nicotine acts on developing neurocircuitry in adolescence to promote later addiction vulnerability remains largely unknown, but may hold the key for informing more effective intervention efforts. We found transient nicotine exposure in early adolescent (PND 21-28) male mice was sufficient to produce a marked vulnerability to nicotine in adulthood (PND 60 + ), associated with disrupted functional connectivity in dopaminergic circuits. These mice showed persistent adolescent-like behavioral and physiological responses to nicotine, suggesting that nicotine exposure in adolescence prolongs an immature, imbalanced state in the function of these circuits. Chemogenetically resetting the balance between the underlying dopamine circuits unmasked the mature behavioral response to acute nicotine in adolescent-exposed mice. Together, our results suggest that the perseverance of a developmental imbalance between dopamine pathways may alter vulnerability profiles for later dopamine-dependent psychopathologies.

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