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

Abstract

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 dopamine 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 dopamine 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 raclopride, a D 2 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 dopamine autoreceptors over short-term neuroadaptation of dopamine release involves both inhibitory and paradoxically, facilitatory components.

Effect of Cocaine on Fas-Associated Protein with Death Domain in the Rat Brain: Individual Differences in a Model of Differential Vulnerability to Drug Abuse

“…Similarly, the stimulation of D 2 , but not D 1 , DA receptors induced a marked increase in FGF-2 expression in the striatum and cortex (Roceri et al, 2001;Fumagalli et al, 2003). The present study also showed that D 1 DA (Kita et al, 2007) demonstrate that D 2 receptors provide a presynaptic component that can not only modulate autoinhibition, but also short-term facilitation of DA release, therefore impacting both D 1 -and D 2 -mediated postsynaptic plasticity. As for how D 2 signal transduction mechanisms modulate FADD activation, it has been previously described that activation of the D 2 receptors can activate ERK (Luo et al, 1998;Yan et al, 1999) and also that FADD modulation by opiate drugs was dependent on the activation of the antiapoptotic ERK1/2 signaling pathway (Garcia-Fuster et al, 2007), which suggests ERK as a possible mediator of FADD modulation after D 2 receptor activation by cocaine.…”

Disulfiram stimulates dopamine release from noradrenergic terminals and potentiates cocaine-induced dopamine release in the prefrontal cortex

“…Consistent with this hypothesis, disulfiram-induced increase in extracellular DA was reversed in both cortices by the local perfusion of the sodium channel inhibitor TTX, confirming that DA was released via a nerve impulse mediated exocytotic process, as well as by the systemic administration of clonidine, consistent with the ability of α 2 -agonists to suppress noradrenergic activity (Svensson et al 1975), but was not reduced by the D 2 agonist quinpirole, in spite of its ability to inhibit dopaminergic activity (White and Wang 1984;Kita et al 2007). …”

Methylphenidate Modifies Overflow and Presynaptic Compartmentalization of Dopamine via an α-Synuclein-Dependent Mechanism

“…Repeated-burst stimulation of the MFB at frequencies of 20 to 50 Hz facilitates DA overflow in the dorsal striatum in mice and rats in such a way that more DA is released after subsequent stimuli than that observed after the first stimulus (Yavich, 1996;Yavich and MacDonald, 2000;Kita et al, 2007). A working model shown in Fig.…”