Sustained high release at rapid stimulation rates and reduced functional autoreceptors characterize prefrontal cortex dopamine terminals.

The release of dopamine (DA) from mesocortical and nigrostriatal nerve terminal fields, as well as its modulation by auto- and heteroreceptors was investigated. Rabbit brain slices obtained from medial prefrontal cortex (PFC) and nucleus caudate (striatum) were prelabeled with [3H]DA in the presence of 0.3 microM desipramine. Neuronal depolarization was elicited by electrical stimulation. Higher stimulation-evoked overflow of [3H]DA (release) was observed from PFC than from striatal slices. At 0.3 Hz (120 pulses) release from the PFC was 60% higher than from the striatum, and at higher frequencies (10 Hz and 120 or 1200 pulses) the fraction of tissue radioactivity released from the PFC was 550% greater than that released from the striatum. These differences were not eliminated by blockade of autoreceptors with haloperidol, or by inhibition of neuronal uptake with nomifensine. These results suggest that the coupling between neuronal depolarization and DA release is more efficient in the PFC than in the striatum. This may allow the PFC terminals to sustain neurotransmission under continuous fast firing. Selective D2 agonists, as well as nonselective DA agonists, inhibited DA release in a concentration-dependent fashion from the PFC and the striatum. Their effects were blocked by l-sulpiride or haloperidol. SKF 38393, a selective D1 agonist, produced a small facilitation of release from both regions; its effects were blocked by SCH 23390 (a selective D1 antagonist). The latter was ineffective on its own. The maximal degree of inhibition of release produced by apomorphine, bromocriptine and LY-171555 was lower in the PFC than in the striatum; these differences were accentuated greatly at high stimulation rates. When the slices were stimulated at frequencies comparable to the "in vivo" firing rates for each neuronal group, apomorphine and LY-171555 were much weaker in inhibiting DA release from the PFC (10 Hz) than from the striatum (3 Hz). In the striatum, strong modulation of DA release by endogenous DA was observed; whereas little modulation was seen in the PFC. Nomifensine produced larger increases in the stimulation-evoked overflow of DA from PFC and there was no synergistic interaction between nomifensine and haloperidol in this structure. In the striatum, marked facilitation of DA overflow was observed when nomifensine and haloperidol were given together. Furthermore, haloperidol per se facilitated DA release from both brain regions; however, the degree of facilitation was frequency dependent in the striatum, but not in the PFC.(ABSTRACT TRUNCATED AT 400 WORDS)