Nicotine's Effects on Schizophrenia-like Symptoms in a Mice Model: Time Matters.
Ana Carolina Dutra-Tavares, Luciana Araújo Couto, Thainá P Souza, Anais Bandeira-Martins, Juliana Oliveira Silva, Claudio C Filgueiras, Anderson Ribeiro-Carvalho, Alex C Manhães, Yael Abreu-Villaça
Brain sciences August 25, 2024 DOI: 10.3390/brainsci14090855 via PubMed
Summary
AI-generated from the abstractIn a mouse model of schizophrenia induced by phencyclidine, the order in which nicotine (a surrogate for smoking) is introduced matters for the behavioral outcomes. Nicotine given before phencyclidine potentiated locomotor sensitization, a behavior linked to psychosis. Nicotine given after phencyclidine worsened a schizophrenia-like deficit in pre-pulse inhibition, but only in male mice. Neither sequence affected rearing, a control behavior. The findings suggest that whether smoking precedes schizophrenia or vice versa produces distinct effects on the brain and behavior, which may help identify mechanisms underlying the high comorbidity between smoking and schizophrenia.
Study at a glance
| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | C57Bl/6 mice |
| Interventions | Nicotine Phencyclidine |
| Duration | 4 days of single exposure followed by 5 days of combined exposure |
| Keywords | E-cigarette Nmda receptor antagonism Comorbidity Positive symptoms Pre-pulse inhibition |
| Key finding | The sequence of nicotine and phencyclidine exposure differentially affects schizophrenia-relevant behaviors in mice, with nicotine priming potentiating phencyclidine-evoked sensitization and nicotine after phencyclidine worsening pre-pulse inhibition deficits in males. |
Abstract
Tobacco consumption in schizophrenia (SCHZ) patients is highly prevalent. Data support the occurrence of sequential events during comorbidity establishment, and both smoking first, SCHZ second and SCHZ first, smoking second sequences have been proposed. To investigate whether these two possibilities lead to distinct outcomes of comorbidity, we used a phencyclidine-induced SCHZ model and nicotine exposure as a surrogate of smoking. C57Bl/6 mice were submitted to a protocol that either began with 4 days of phencyclidine exposure or 4 days of nicotine exposure. This period was followed by 5 days of combined phencyclidine + nicotine exposure. Locomotor sensitization and pre-pulse inhibition (PPI) were assessed due to their well-known associations with SCHZ as opposed to rearing, an unrelated behavior. Nicotine priming potentiated phencyclidine-evoked sensitization. However, nicotine exposure after SCHZ modeling did not interfere with phencyclidine's effects. In the PPI test, nicotine after SCHZ modeling worsened the phencyclidine-evoked deficiency in males. In contrast, nicotine priming had no effects. Regarding rearing, nicotine priming failed to interfere with phencyclidine-mediated inhibition. Similarly, phencyclidine priming did not modify nicotine-mediated inhibition. The present results indicate that the sequence, either SCHZ-first or nicotine-first, differentially impacts comorbidity outcomes, a finding that is relevant for the identification of mechanisms of nicotine interference in the neurobiology of SCHZ.