期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 456, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2022.116282
关键词
Psychosis; Positive symptoms; Tobacco; Prodrome; Adolescence
资金
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES-BRAZIL) [001]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq-BRAZIL)
- Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ-BRAZIL)
- FAPERJ-BRAZIL [SEI-260003/001135/2020, E-26/200.957/2021, E-26/202.266/2018]
- CNPq-BRAZIL [304332/2016-0, 304368/2020-2]
The association between schizophrenia and nicotine addiction is evident during adolescence. Nicotine may ameliorate psychotic-like behavior in adolescent mice, possibly through mechanisms involving D2 receptors.
The association between schizophrenia and nicotine addiction becomes evident during adolescence. Here, to investigate interactive events that might underlie the early establishment of this comorbidity, we used phencyclidine-evoked locomotor sensitization, a proxy model of psychotic behavior, and nicotine minipump infusions in adolescent mice. Considering the involvement of dopamine D2 receptors in both schizophrenia and addiction, we further tested their role by exposing mice to raclopride. Adolescent mice that were either exposed to nicotine (24 mg/Kg/day) or not, received single daily raclopride (0.5 mg/kg, s.c.) or saline followed by phencyclidine injections (10 mg/Kg, s.c.) during open field testing for 6 consecutive days (Acquisition phase, ACQ). Phencyclidine and nicotine challenges (Sensitization Test, ST) were carried out after a 5-day withdrawal. Ambulation escalated in response to repeated phencyclidine exposure during ACQ and was increased after phencyclidine challenge, evidencing development and expression of locomotor sensitization. Raclopride pre-vented phencyclidine-evoked development of sensitization. However, raclopride pre-exposure during ACQ only shortened its expression in phencyclidine-challenged mice. Nicotine failed to interfere with phencyclidine stimulatory effects during ACQ but potentiated raclopride inhibition during the first ACQ days. During ST, nicotine history shortened the expression of phencyclidine-evoked sensitization. Nicotine challenge had no impact on locomotion, which is consistent with a lack of nicotine/phencyclidine cross-sensitization. In conclu-sion, our results show that nicotine does not worsen, and may even ameliorate phencyclidine-sensitized psy-chotic-like behavior in adolescent mice. The potentiation of raclopride-mediated inhibition further suggests that nicotine transiently improves the therapeutic efficacy of medication on psychotic symptoms through mechanisms that converge on D2 receptors.
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