Neurobehavioral correlates of dopamine agonist-induced eye-blinking in the marmoset monkey

Eye-blinking has been used to catalog dopaminergic receptor subtype activation in several mammalian species. In this study, the dissimilar effects of directly-acting D₁ and D₂ agonists and an indirectly-acting non-selective agonist (SKF-82958, quinelorane, cocaine, respectively) on eye-blinking were confirmed in marmosets. Subsequently, functional magnetic resonance imaging (fMRI) was used to examine their effects on functional connectivity (FC) between the dopamine-rich putamen and other brain regions. Results indicate that SKF-82958 produced dose-dependent increases in blinking, with the highest dose (0.3 mg/kg) yielding > 9-fold increases over baseline values. In contrast, the highest dose of quinelorane (0.001 mg/kg) reduced blink rates to ∼30 % of baseline. Following the highest dose of cocaine (5.6 mg/kg), only limited (∼20 %) and short-lived (∼20-min) decreases in eye-blinking were observed. In fMRI studies, cocaine induced transient FC increases between putamen and striatal regions, whereas the D₁ and D₂ agonists induced distinct temporal dynamics and region-specific changes in putamen FC. SKF-82958 strengthened putamen FC with motor and sensory regions and reduced FC with visual and cerebellar regions. Conversely, quinelorane reduced putamen connectivity with motor and sensory areas and strengthened FC with regions associated with visual and emotional regulation. These effects in marmosets align with previous outcomes and show that dopamine receptor-subtype activation produce distinct patterns of FC between the putamen and brain regions that play key integrative roles in eye-blinking and other behavior. These findings support eye-blinking as a non-invasive cross-species indicator of dopaminergic subtype activation that can be used to enhance our understanding of dopamine-related dysfunction in neuropsychiatric disorders.