Factors influencing JUUL e-cigarette nicotine vapour-induced reward, withdrawal, pharmacokinetics and brain connectivity in rats: sex matters.

Though vaping likely represents a safer alternative to smoking, it is not without risks, many of which are not well understood, especially for vulnerable populations. Here we evaluate the sex- and age-dependent effects of JUUL nicotine vapour in rats. Following passive nicotine vapour exposures (from 59 mg/ml JUUL nicotine pods), rats were evaluated for reward-like behaviour, locomotion, and precipitated withdrawal. Pharmacokinetics of nicotine and its metabolites in brain and plasma and the long-term impact of nicotine vapour exposure on functional magnetic resonance imaging-based brain connectivity were assessed. Adult female rats acquired conditioned place preference (CPP) at a high dose (600 s of exposure) of nicotine vapour while female adolescents, as well as male adults and adolescents did not. Adult and adolescent male rats displayed nicotine vapour-induced precipitated withdrawal and hyperlocomotion, while both adult and adolescent female rats did not. Adult females showed higher venous and arterial plasma and brain nicotine and nicotine metabolite concentrations compared to adult males and adolescent females. Adolescent females showed higher brain nicotine concentration compared to adolescent males. Both network-based statistics and between-component group connectivity analyses uncovered reduced connectivity in nicotine-exposed rats, with a significant group by sex interaction observed in both analyses. The short- and long-term effects of nicotine vapour are affected by sex and age, with distinct behavioural, pharmacokinetic, and altered network connectivity outcomes dependent on these variables.

Diffusion-weighted MRI in neurodegenerative and psychiatric animal models: Experimental strategies and main outcomes.

Preclinical MRI approaches constitute a key tool to study a wide variety of neurological and psychiatric illnesses, allowing a more direct investigation of the disorder substrate and, at the same time, the possibility of back-translating such findings to human subjects. However, the lack of consensus on the optimal experimental scheme used to acquire the data has led to relatively high heterogeneity in the choice of protocols, which can potentially impact the comparison between results obtained by different groups, even using the same animal model. This is especially true for diffusion-weighted MRI data, where certain experimental choices can impact not only on the accuracy and precision of the extracted biomarkers, but also on their biological meaning. With this in mind, we extensively examined preclinical imaging studies that used diffusion-weighted MRI to investigate neurodegenerative, neurodevelopmental and psychiatric disorders in rodent models. In this review, we discuss the main findings for each preclinical model, with a special focus on the analysis and comparison of the different acquisition strategies used across studies and their impact on the heterogeneity of the findings.