Repeated exposure to high-dose nicotine induces prefrontal gray matter atrophy in adolescent male rats.
Study Goal
The researchers aimed to investigate the effects of repeated high-dose nicotine treatment on brain anatomy and behavior in adolescent and adult male rats.
Results Summary
Nicotine treatment in adolescent rats led to reduced gray matter volume in the medial prefrontal cortex (mPFC), increased oxidative stress, elevated microglial activity, and altered synaptic markers, suggesting structural and connectivity deficits. Adult rats showed abolished body weight gain but no significant brain changes.
Population
Adolescent and adult male rats.
Effective Dosage
2 mg/kg body weight daily.
Duration
15 days.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
15-day repeated nicotine treatment at a daily dose of 2 mg/kg body weight | decrease | body weight gain | adult male rats | - | abolished | #1 |
15-day repeated nicotine treatment at a daily dose of 2 mg/kg body weight | no change | body weight | adolescent male rats | - | did not affect | #2 |
15-day repeated nicotine treatment at a daily dose of 2 mg/kg body weight | decrease | whole-brain gray matter (GM) volume | adolescent male rats | - | significant reduction | #3 |
15-day repeated nicotine treatment at a daily dose of 2 mg/kg body weight | decrease | regional GM volume in the medial prefrontal cortex (mPFC) | adolescent male rats | - | further reduction | #4 |
15-day repeated nicotine treatment at a daily dose of 2 mg/kg body weight | neutral | GM volume covariations between the mPFC and a number of brain regions | adolescent male rats | - | altered | #5 |
15-day repeated nicotine treatment at a daily dose of 2 mg/kg body weight | decrease | presynaptic marker synaptophysin (SYN) | adolescent male rats | - | significantly decreased expression | #6 |
15-day repeated nicotine treatment at a daily dose of 2 mg/kg body weight | increase | oxidative stress | adolescent male rats | - | significantly increased | #7 |
15-day repeated nicotine treatment at a daily dose of 2 mg/kg body weight | increase | microglial marker ionized calcium binding adaptor molecule 1 (IBA1) | adolescent male rats | - | significantly elevated expressions | #8 |
Incidences of seizure after e-cigarette use in adolescents and young adults have been reported, raising the concern about the risk of nicotine overconsumption. Few previous studies have investigated the effects of nicotine at high doses on brain and behavior in adolescent animals. In this study, the effects of a 15-day repeated nicotine treatment at a daily dose of 2 mg/kg body weight were investigated in adolescent and adult male rats. Nicotine treatment abolished body weight gain in the adults, but did not affect the body weight significantly in the adolescents. Only the nicotine-treated adolescents showed significant changes in brain anatomy 1 day post-treatment, which manifested as a significant reduction of whole-brain gray matter (GM) volume, a further reduction of regional GM volume in the medial prefrontal cortex (mPFC) and altered GM volume covariations between the mPFC and a number of brain regions. The mPFC of nicotine-treated adolescent rats did not exhibit evident signs of neuronal degeneration and reactive astrocytosis, but showed a significantly decreased expression of presynaptic marker synaptophysin (SYN), along with a significantly increased oxidative stress and a significantly elevated expressions of microglial marker ionized calcium binding adaptor molecule 1 (IBA1). Together, these results suggested that repeated nicotine overdosing may shift regional redox, modulate microglia-mediated pruning, and give rise to structural/connectivity deficits in the mPFC of adolescent male rats.