Differences in sensitivity to neuroleptic blockade: medial forebrain bundle versus frontal cortex self-stimulation

The effects of systemic injections of the dopamine receptor antagonist, cis-flupenthixol were tested on intracranial self-stimulation at electrode sites in the medial forebrain bundle and the medial prefrontal cortex. Changes in the reward effectiveness of the brain stimulation were assessed using a curve-shift paradigm. Low to moderate doses of cis-flupenthixol (0.05, 0.1 and 0.15 mg/kg) consistently produced larger upward shifts in the rate-frequency function for medial forebrain bundle than for medial prefrontal self-stimulation. At the highest doses of cis-flupenthixol (0.15 and 0.2 mg/kg), some of the medial forebrain bundle rats failed to respond, whereas all medial prefrontal rats responded at these doses. These results demonstrate that medial forebrain bundle self-stimulation is much more dependent on dopamine systems than is prefrontal cortex self-stimulation.