Effects of Novel Dopamine D4 Receptor-Targeted Compounds on locomotor activity and Anxiety-Like Behavior in Male and Female Sprague Dawley Rats

The consequences of modulating subtypes of G protein coupled dopamine receptors are broadly studied for their role in decision making behavior, specifically in situations involving uncertain risk and reward. The actions of dopamine D4 receptors (D4Rs) on these complex processes are the least understood, particularly due to a lack of available compounds with suitable selectivity for D4Rs. Further, current research often fails to evaluate how modulating specific dopamine receptor subtypes may affect locomotor activity and anxiety-like behavior as confounding factors prior to assessing their function in behavioral assays of higher order decision making. The goal of the current study was to evaluate the extent that D4R modulation contributes to locomotor and anxiety-like behavioral measures and serve as potential confounding variables when evaluated in future experiments that will assay more complex risk/reward decision making behaviors. As such, the current report utilized the open-field test to assess the effects of novel and selective D4 receptor targeted compounds; a full antagonist (FMJ-054), a high-efficacy partial agonist (FMJ-038), and a low-efficacy partial agonist (FMJ-045) on locomotor activity and anxiety-like behavior in male and female Sprague Dawley rats.