Paradoxical modulation of short-term facilitation of dopamine release by dopamine autoreceptors

Electrophysiological studies have demonstrated that dopaminergic neurons burst fire during certain aspects of rewardrelated behavior; however, the correlation between dopamine release and cell firing is unclear. When complex stimulation patterns that mimic intracranial self -stimulation were employed, dopamine release was shown to exhibit facilitated as well as depressive components (Montague et al. 2004). Understanding the biological mechanisms underlying these variations in dopamine release is necessary to unravel the correlation between unit activity and neurotransmitter release. The dopamine autoreceptor provides negative feedback to cloparnine release, inhibiting release on the time scale of a few seconds. Therefore, we investigated this D-2 receptor to see whether it is one of the biological mechanisms responsible for the history-dependent modulation of dopamine release. Striatal cloparnine release in anesthetized rats was evoked with stimulus trains that were designed to promote the variability of dopamine release. Consistent with the well established D-2-mediated autoinhibition, the short-term depressive component of dopamine release was blocked by raclopricle, a D2 antagonist, and enhanced by quinpirole, a D-2-receptor agonist. Surprisingly, these same drugs exerted a similar effect on the short-term facilitated component: a decrease with raclopride and an increase with quinpirole. These data demonstrate that the commanding control exerted by doparnine autoreceptors over short-term neuroadaptation of dopamine release involves both inhibitory and paradoxically, facilitatory components.