Adolescent nicotine induces depressive and anxiogenic effects through ERK 1-2 and Akt-GSK-3 pathways and neuronal dysregulation in the nucleus accumbens.
Addict Biol
; 26(2): e12891, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-32135573
ABSTRACT
Long-term tobacco dependence typically develops during adolescence and neurodevelopmental nicotine exposure is associated with affective disturbances that manifest as a variety of neuropsychiatric comorbidities in clinical and preclinical studies, including mood and anxiety-related disorders. The nucleus accumbens shell (NASh) is critically involved in regulating emotional processing, and both molecular and neuronal disturbances in this structure are associated with mood and anxiety-related pathologies. In the present study, we used a rodent model of adolescent neurodevelopmental nicotine exposure to examine the expression of several molecular biomarkers associated with mood/anxiety-related phenotypes. We report that nicotine exposure during adolescence (but not adulthood) induces profound upregulation of the ERK 1-2 and Akt-GSK-3 signalling pathways directly within the NASh, as well as downregulation of local D1R expression that persists into adulthood. These adaptations were accompanied by decreases in τ, α, ß, and γ-band oscillatory states, hyperactive medium spiny neuron activity with depressed bursting rates, and anxiety and depressive-like behavioural abnormalities. Pharmacologically targeting these molecular and neuronal adaptations revealed that selective inhibition of local ERK 1-2 and Akt-GSK-3 signalling cascades rescued nicotine-induced high-γ-band oscillatory signatures and phasic bursting rates in the NASh, suggesting that they are involved in mediating adolescent nicotine-induced depressive and anxiety-like neuropathological trajectories.
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Base de dados:
MEDLINE
Assunto principal:
Ansiedade
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Quinase 3 da Glicogênio Sintase
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Depressão
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Nicotina
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Núcleo Accumbens
Limite:
Adolescent
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Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article