Post adversity changes in nigro-striatal dopamine: A mechanism for anxiety induced exacerbated innate repetitive behaviors

Abstract Anxiety exacerbates symptoms in various psychiatric disorders. In conditions such as obsessive-compulsive disorder (OCD) or Tourette syndrome, anxiety intensifies stereotypic and repetitive behaviors. Rodent self-grooming, a structured, repetitive innate behavior, serves as an effective rodent platform for studying these behaviors in neuropsychiatric research. Anxiety is also linked to altered functioning of the dopamine (DA) system, particularly within the substantia-nigra pars compacta (SNc), the main DA source to the dorsal striatum through the nigro-striatal pathway. Striatal modulation by DA signal also plays a complex role in repetitive behaviors and OCD-like symptoms, suggesting this system as linking anxiety to the induced exacerbation of repetitive behavior. In the present study, we observed several long-term effects of anxiety inducing foot shock on grooming behavior. Recordings single unit neuronal activity in the SNc revealed distinct response patterns related to grooming behavior with changes in the magnitude and timing following the shock treatment. Notably, DA neurons of different nigro-striatal pathways demonstrated different changes in different response pattern type units. DA neurons projecting to the dorsolateral striatum (DLS) showed increase, while those targeting the dorsomedial striatum (DMS) exhibited decrease in transient activity -suggesting a shift in cortico-striatal circuitry of behavioral control. These neural changes were correlated with the observed behavioral alterations following adversity. Furthermore, targeted stimulation of DLS-projecting DA neurons rescued the anxiety-induced behavioral effects, highlighting the critical role of the nigro-striatal pathway to the DLS in mediating the interaction between anxiety and repetitive behaviors, thus offering future direction for mitigation of relevant psychiatric symptoms.