Receptor Subtypes Involved in the Presynaptic and Postsynaptic Actions of Dopamine on Striatal Interneurons

Abstract

By stimulating distinct receptor subtypes, dopamine (DA) exerts presynaptic and postsynaptic actions on both large aspiny (LA) cholinergic and fast-spiking (FS) parvalbumin-positive interneurons of the striatum. Lack of receptor- and isoform-specific pharmacological agents, however, has hampered the progress toward a detailed identification of the specific DA receptors involved in these actions. To overcome this issue, in the present study we used four different mutant mice in which the expression of specific DA receptors was ablated. In D1 receptor null mice, D1R-/-, DA dose-dependently depolarized both LA and FS interneurons. Interestingly, SCH 233390 (10 microm), a D1-like (D1 and D5) receptor antagonist, but not l-sulpiride (3-10 microm), a D2-like (D2, D3, D4) receptor blocker, prevented this effect, implying D5 receptors in this action. Accordingly, immunohistochemical analyses in both wild-type and D1R-/- mice confirmed the expression of D5 receptors in both cholinergic and parvalbumin-positive interneurons of the striatum. In mice lacking D2 receptors, D2R-/-, the DA-dependent inhibition of GABA transmission was lost in both interneuron populations. Both isoforms of D2 receptor, D2L and D2S, were very likely involved in this inhibitory action, as revealed by the electrophysiological analysis of the effect of the DA D2-like receptor agonist quinpirole in two distinct mutants lacking D2L receptors and expressing variable contents of D2S receptors. The identification of the receptor subtypes involved in the actions of DA on different populations of striatal cells is essential to understand the circuitry of the basal ganglia and to develop pharmacological strategies able to interfere selectively with specific neuronal functions.

Dopaminergic Modulation of Axon Collaterals Interconnecting Spiny Neurons of the Rat Striatum

“…With this method, a presynaptic D 2 -mediated modulation similar to that shown on the striatopallidal pathway (Cooper and Stanford, 2001;Mengual and Pickel, 2002) or in the cholinergic or fastspiking (FS) interneurons (Pisani et al, 2000;Momiyama and Koga, 2001;Centonze et al, 2003) was shown. Similarly, a presynaptic modulation by D 1 receptor agonists as that reported in the striatonigral pathway (Floran et al, 1990(Floran et al, , 1997Cameron and Williams, 1993;Radnikow and Misgeld, 1998) was also shown, despite postsynaptic dopaminergic actions (Pacheco-Cano et al, 1996) on the subthreshold inward rectification Nisenbaum and Wilson, 1995;Mermelstein et al, 1998;Farries and Perkel, 2000) that shunts inhibitory inputs (Fitzpatrick et al, 2001).…”

“…A dopaminergic modulation should be seen as consistent, however, even after intrastriatal field stimulation, if its presence is somehow ubiquitous or predominant (Pisani et al, 2000;Mo-miyama and Koga, 2001;Centonze et al, 2003). Otherwise, modulation would be concealed by the mixed source of differentially modulated inputs (Fitzpatrick et al, 2001).…”

“…The latter responses are likely to be variable because they come from a mixed source of GABAergic terminals: several classes of interneurons and recurrent axon collaterals (Kita, 1993;Jaeger et al, 1994;Kawaguchi et al, 1995;Koos and Tepper, 1999;Fitzpatrick et al, 2001). In case all interneuron types do not respond in the same manner to different classes of dopamine receptor agonists (Aosaki et al, 1998;Bracci et al, 2002;Centonze et al, 2002Centonze et al, , 2003Yasumoto et al, 2002;Gao et al, 2003), it is expected that variety will make this mixed source inconsistent when responding to the agonists. In contrast, if antidromic stimulation from the pallidum evokes IPSCs from a single source (i.e., axon collaterals), then the responses in this case are likely to be more consistent.…”

Substantia nigra dopaminergic neurons and striatal interneurons are engaged in three parallel but interdependent postnatal neurotrophic circuits

“…Favoring the second option is the report that, after binding to D 2 receptors, dopamine can be internalized to form a signaling complex (including ß‐arrestin and protein phosphatase 2) that regulates the Akt pathway (Beaulieu et al, 2008), a cascade involved in neuroprotection (Dudek et al, 1997; Soler et al, 1999). Dopamine inhibits GABA A ‐mediated synaptic inputs to intrinsic striatal neurons (Bracci, Centonze, Bernardi, & Calabresi, 2002; Momiyama & Koga, 2001; Pisani, Bonsi, Centonze, Calabresi, & Bernardi, 2000) through presynaptic D 2 receptors (Centonze et al, 2003; for a review, see Berke, 2011). All together, we speculate that dopamine could be involved in the acute and chronic protection of FS striatal terminals and, therefore, could contribute to long‐term FS survival.…”

A Critical Interaction between Dopamine D2 Receptors and Endocannabinoids Mediates the Effects of Cocaine on Striatal GABAergic Transmission

“…This brain area receives profuse dopaminergic innervation arising from midbrain DA neurons and has a very high density of DA receptors (Mansour and Watson, 1995;Surmeier et al, 1996;Centonze et al, 2003). Cocaine increases DA release in the striatum through the blockade of transporter-mediated DA reuptake from nigrostriatal nerve endings and causes rapid induction of striatal c-fos, a commonly used molecular marker for neuronal activity.…”