Background: Psychostimulants are commonly used to treat attentional deficits, which are conditions that implicate disturbances in dopaminergic (DA) function. However, the success rate of treating such conditions in cognitive diseases is limited, thus necessitating a better understanding of stimulant drugs and their effects on attentional impairment. Recent studies have shown that astrocytes respond to DAergic release in the brain. The role of astroglia in synaptic function and the regulation of behaviour has been found to take part in underlying behavioural impairments of psychiatric disorders in striatal regions.
Methods: Fibre photometry (FP) was validated as a method to measure in vivo DA release in the caudate putamen (CPu), a region that represents the human dorsal striatal region of rats, during a Signal Detection Task (SDT). Rats were segregated into low versus high performers based on their measured accuracy on an SDT, where their performances were analysed before and after being given dextroamphetamine (d-AMPH) to investigate their attentional differences. Their brains were analysed using immunohistochemistry (IHC), where the count of astrocytes was analysed in the CPu by using glial fibrillary astrocyte protein antibodies.
Results: Only low performers showed an improvement in attentional accuracy after given d-AMPH. All rats’ performances worsened in the presence of a distractor, with the high performers being the most affected by this intervention. IHC results showed that low performers had a significantly higher count of astrocytes in the CPu compared to high performers, which suggests that a higher count of astrocytes in the CPu may underlie impaired fronto-striatal executive control over attention. FP measurements showed that DA levels could be measured during an SDT task, and that it increased when DA-increasing stimuli was introduced.
Conclusion: The main findings of this project indicate that astrocytic dysregulation in the CPu of rats may underlie impaired attentional performance. Since astrocytes express the high-affinity dopamine transporter (DAT), the primary target of stimulants used clinically to treat attention-deficit hyperactivity disorder (ADHD), these findings offer a tantalizing novel mechanism to explain the therapeutic efficacy of medications in ADHD. Furthermore, Successful FP measurements indicate its potential in pharmacological analyses, which would enhance the understanding of attention dysfunctions and individual differences in performance.
2023.