Dopamine receptor blockade in the rat medial prefrontal cortex reduces spontaneous and amphetamine-induced activity and does not affect prepulse inhibition

The functions and interactions of cortical and subcortical dopamine systems are of interest because alterations in these systems have been implicated in neuropsychiatric diseases, such as schizophrenia. It has been proposed that prefrontal dopamine transmission may oppose dopamine transmission in subcortical sites, such as the nucleus accumbens. Accordingly, reduced prefrontal dopamine transmission would be expected to enhance or induce behavioral effects that have been associated with stimulation of accumbal dopamine receptors. In rats, spontaneous and amphetamine-induced activity is supported by dopamine receptor stimulation in the nucleus accumbens, while prepulse inhibition (PPI) of the acoustic startle response, which is used to measure sensorimotor gating and is disrupted in schizophrenia, is reduced by increased accumbal dopamine receptor stimulation. In the present experiments, we found that bilateral infusion of the dopamine D₁/D₂ receptor antagonist cis-flupenthixol dihydrochloride into the medial prefrontal cortex of Wistar rats (25 μg each side) reduced spontaneous activity and completely blocked induction of hyperactivity by systemic administration of D-amphetamine sulfate (1 mg/kg), while not affecting PPI. These findings do not support an antagonism between prefrontal and accumbal dopamine in the control of behavior. Rather, our data demonstrate that prefrontal dopamine transmission may modulate some behavioral processes in a similar way to accumbal dopamine.