Adolescent vulnerability to anxiety: a dopamine story

Anxiety disorders are a major worldwide public health concern, with ~1 in 4 Australians suffering from a clinically diagnosed anxiety disorder at least once in their lifetime.

Aims

Our lab aims to characterize the neurobiological factors that underlie this age-related vulnerability, in order to assist in the development of more effective therapeutic interventions for young people.

The aim of this project is to investigate potential age-related differences in the activation of D1R vs D2R in the PFC of adult vs adolescent mice following extinction.

This project will also examine the effect of the D2 partial agonist Aripiprazole on extinction consolidation and D1R/D2R activation in the PFC.

While these disorders can affect people of all ages, adolescence represents a particularly vulnerable period for onset. The most commonly used preclinical model for studying anxiety disorders in rodents is a fear conditioning paradigm. Using this model, we have shown that inhibition of learned fear, known as extinction, is less effective in postnatal day (P)35 (adolescent) compared to P70 (adult) rats due to maturational differences in the prefrontal cortex (PFC). This difference may be due to the disrupted balance of dopamine receptor 1 (DR1) vs 2 (DR2) signaling during adolescence, however this has yet to be directly demonstrated.

This project employs mice that express green fluorescent protein-(GFP) tagged D1R and D2R, as well as Fos/GFP immunohistochemistry to identify activated D1R and D2R neurons.