Rationale Previously we demonstrated reduced D_2/3 receptor availability in the ventral striatum of hyper-impulsive rats on the five-choice serial reaction time task (5-CSRTT). However, the anatomical locus of D_2/3 receptor dysfunction in high impulsive (HI) rats is unknown. Objective In the present study, we investigated whether D_2/3 receptor dysfunction in HI rats is localised to the core or shell sub-regions of the nucleus accumbens (NAcb). Methods Rats were selected for low (low impulsive, LI) and high impulsivity on the 5-CSRTT and implanted with guide cannulae targeting the NAcb core and shell. The D_2/3 receptor agonist quinpirole was locally injected in the NAcb (0.1, 0.3 and 1 μg per infusion) and its effects investigated on the performance of LI and HI rats on the 5-CSRTT as well as spontaneous locomotor activity in an open field. Results Intra-NAcb core quinpirole increased premature responding in HI rats but not in LI rats. In contrast, intra-NAcb shell quinpirole strongly increased locomotor activity in HI rats, unlike LI rats. This effect was blocked by intra-NAcb shell infusions of the D_2/3 receptor antagonist nafadotride (0.03 μg). However, nafadotride was ineffective in blocking the effects of intra-NAcb core quinpirole on premature responding in HI rats. Conclusions These findings indicate that impulsivity and hyperactivity are separately regulated by core and shell sub-regions of the NAcb and that HI rats show an enhanced response to D_2/3 receptor activation in these regions. These results suggest that the symptom clusters of hyperactivity and impulsivity in attention-deficit hyperactivity disorder may be neurally dissociable at the level of the NAcb.

Exposure to organophosphates (OPs) can lead to cognitive deficits and oxidative damage. Little is known about the relationship between behavioral deficits and oxidative stress within the context of such exposures. Accordingly, the first experiment was carried out to address this issue. Male Wistar rats were administered 250mg/kg of chlorpyrifos (CPF), 1.5mg/kg of diisopropylphosphorofluoridate (DFP), or 15mg/kg of parathion (PTN). Spatial learning in the water maze task was evaluated, and F₂-isoprostanes (F₂-IsoPs) and prostaglandin (PGE₂) were analyzed in the hippocampus. A second experiment was designed to determine the degree of inhibition of brain acetylcholinesterase (AChE) activity, both the soluble and particulate forms of the enzyme, and to assess changes in AChE gene expression given evidence on alternative splicing of the gene in response to OP exposures. In addition, brain acylpeptide hydrolase (APH) activity was evaluated as a second target for OP-mediated effects. In both experiments, rats were sacrificed at various points to determine the time course of OPs toxicity in relation to their mechanism of action. Results from the first experiment suggest cognitive and emotional deficits after OPs exposure, which could be due to, at least in part, increased F₂-IsoPs levels. Results from the second experiment revealed inhibition of brain AChE and APH activity at various time points post OP exposure. In addition, we observed increased brain read-through splice variant AChE (AChE-R) mRNA levels after 48h PTN exposure. In conclusion, this study provides novel data on the relationship between cognitive alterations and oxidative stress, and the diverse mechanisms of action along a temporal axis in response to OP exposures in the rat.

This review highlights the significant impact of air quality, specifically particulate matter (PM), on cognitive decline and age-related diseases in the elderly. Despite established links to other pathologies, such as respiratory and cardiovascular illnesses, there is a pressing need for increased attention to the association between air pollution and cognitive aging, given the rising prevalence of neurocognitive disorders. PM sources are from diverse origins, including industrial activities and combustion engines, categorized into PM₁₀, PM_2.5, and ultrafine PM (UFPM), and emphasized health risks from both outdoor and indoor exposure. Long-term PM exposure, notably PM_2.5, has correlated with declines in cognitive function, with a specific vulnerability observed in women. Recently, extracellular vesicles (EVs) have been explored due to the interplay between them, PM exposure, and human aging, highlighting the crucial role of EVs, especially exosomes, in mediating the complex relationship between PM exposure and chronic diseases, particularly neurological disorders. To sum up, we have compiled the pieces of evidence that show the potential contribution of PM exposure to cognitive aging and the role of EVs in mediating PM-induced cognitive impairment, which presents a promising avenue for future research and development of therapeutic strategies. Finally, this review emphasizes the need for policy changes and increased public awareness to mitigate air pollution, especially among vulnerable populations such as the elderly.