The effects of a dopamine D3 antagonist on the comorbidity of PTSD and alcohol consumption in a rodent model

The dopamine D3 receptor has been implicated in the expression of conditioned fear and reward-seeking behavior in animal models. Previous studies have demonstrated that administration of a D3 receptor antagonist can reduce reward-seeking behaviors for nicotine, cocaine, heroin, and alcohol. The administration of a D3 receptor antagonist has also been shown to decrease the expression of conditioned fear in rodents. However, few studies have investigated the role of the D3 antagonism in comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder. The purpose of this study was to examine the effects of the D3 antagonist, SB-277011A, on alcohol consumption in a rodent model of PTSD. A modified single-prolonged stress (SPS) protocol paired with a tone was used to induce PTSD-like behaviors in male Sprague Dawley rats. The modified SPS procedure involved 20 minutes of forced swim, 2 hours of restraint, and 20 minutes of interval foot shock. The acquisition of PTSD-like behaviors and expression of conditioned fear were measured using freeze tests in a novel environment with re-exposure to the tone paired with stressful stimuli. Rats subjected to the modified SPS procedure did not exhibit a significant increase in alcohol consumption. Following the establishment of post-SPS baseline saline injection drinking levels, the administration of 6 mg/kg i.p. of SB-277011A significantly attenuated alcohol consumption in rats exposed to SPS but not the unexposed control rats. These results demonstrated that administration of a D3 antagonist attenuated alcohol consumption in SPS rats but not control rats. Our study implicates the involvement of the dopamine D3 receptor in both reward and conditioned fear and suggests that D3 antagonists may possess therapeutic effects for the management of comorbid PTSD and alcoholism