Dopamine D2/D3 receptor agonists attenuate PTSD-like symptoms in mice exposed to single prolonged stress

Abstract Medications that enhance dopaminergic neurotransmission can be useful in the pharmacotherapy of posttraumatic stress disorder (PTSD), which manifests as fearful memory retrieval, anxiety and depression. We examined the effects of subchronic (15 days) treatment with select dopaminergic medications, including bromocriptine, modafinil, dihydrexidine, rotigotine and pramipexole, in a mouse model of PTSD induced by single prolonged stress (mSPS). The potential antidepressant-like and anxiolytic effects of the medications were measured by the forced swim test (FST) and the elevated plus maze (EPM) test, respectively. In addition, we studied the effects of these medications on memory retrieval in an auditory fear conditioning (FC) test, on ultrasonic vocalizations (USVs) induced by restraint stress, and on spontaneous locomotor activity (SLA). We report that a single exposure to a severe and complex set of stressors several days before testing increased immobility time in the FST and freezing in the FC paradigm and reduced the time spent in the open arms of the EPM. The stressed mice also displayed increased USVs, especially the short type. While none of the tested dopamine-mimetics exhibited anxiolytic-like effects, rotigotine produced antidepressant-like activity specifically in the mSPS-exposed animals. Moreover, both rotigotine and pramipexole shortened the duration of freezing in the fear conditioning test, but only in the mSPS-exposed mice. This study supports the hypothesis that the activation of dopaminergic D2/D3 receptors may be a promising pharmacotherapy for PTSD.