D1-like Dopaminergic Activation of Phosphoinositide Hydrolysis Is Independent of D1A Dopamine Receptors: Evidence from D1A Knockout Mice

Friedman, Eitan; Jin, Liqing; Cai, Guoping; Hollon, Tom; Drago, John; Sibley, David R.; Wang, Hoau-Yan

doi:10.1124/mol.51.1.6

Cited by 119 publications

(85 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Gnal + /À but not in Drd1a + /À Heterozygous Mice Dopamine-stimulated AC activity requires both D1R and Gaolf as indicated by its complete absence in D1R (Friedman et al, 1997) and Gaolf knockout mice . To investigate the consequences of quantitative changes in D1R and Gaolf protein levels on D1R signaling, we used Gnal + /À and Drd1a + /À mice.…”

Section: Dopamine-stimulated Ac Activity Is Decreased Inmentioning

confidence: 95%

Quantitative Changes in Gαolf Protein Levels, but not D1 Receptor, Alter Specifically Acute Responses to Psychostimulants

Corvol

Valjent

Pascoli

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

Striatal dopamine D1 receptors (D1R) are coupled to adenylyl cyclase through Gaolf. Although this pathway is involved in important brain functions, the consequences of quantitative alterations of its components are not known. We explored the biochemical and behavioral responses to cocaine and D-amphetamine (D-amph) in mice with heterozygous mutations of genes encoding D1R and Gaolf (Drd1a + /À and Gnal + /À), which express decreased levels of the corresponding proteins in the striatum. Dopamine-stimulated cAMP production in vitro and phosphorylation of AMPA receptor GluR1 subunit in response to D-amph in vivo were decreased in Gnal + /À, but not Drd1a + /À mice. Acute locomotor responses to D1 agonist SKF81259, D-amph and cocaine were altered in Gnal + /À mice, and not in Drd1a + /À mice. This haploinsufficiency showed that Gaolf but not D1R protein levels are limiting for D1R-mediated biochemical and behavioral responses. Gnal + /À mice developed pronounced locomotor sensitization and conditioned locomotor responses after repeated injections of D-amph (2 mg/kg) or cocaine (20 mg/kg). They also developed normal D-amph-conditioned place preference. The D1R/cAMP pathway remained blunted in repeatedly treated Gnal + /À mice. In contrast, D-amph-induced ERK activation was normal in the striatum of these mice, possibly accounting for the normal development of long-lasting behavioral responses to psychostimulants. Our results clearly dissociate biochemical mechanisms involved in acute and delayed behavioral effects of psychostimulants. They identify striatal levels of Gaolf as a key factor for acute responses to psychostimulants and suggest that quantitative alterations of its expression may alter specific responses to drugs of abuse, or possibly other behavioral responses linked to dopamine function.

show abstract

Section: Dopamine-stimulated Ac Activity Is Decreased Inmentioning

confidence: 95%

Quantitative Changes in Gαolf Protein Levels, but not D1 Receptor, Alter Specifically Acute Responses to Psychostimulants

Corvol

Valjent

Pascoli

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…11). One possibility is that dopamine acts on a putative PLC-linked D1 class DAR (9,10,60). Indeed, SKF83959, a specific agonist for this putative PLC-linked D1 class DAR (11), induced Ca 2ϩ release from intracellular stores in MSN (Fig.…”

Section: Discussionmentioning

confidence: 99%

Dopamine Receptor-mediated Ca2+ Signaling in Striatal Medium Spiny Neurons

Tang

Bezprozvanny

2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Inositol 1,4,5-trisphosphate (InsP 3 ) and cAMP are the two second messengers that play an important role in neuronal signaling. Here, we investigated the interactions of InsP 3 -and cAMP-mediated signaling pathways activated by dopamine in striatal medium spiny neurons (MSN). We found that in ϳ40% of the MSN, application of dopamine elicited robust repetitive Ca 2؉ transients (oscillations). In pharmacological experiments with specific agonists and antagonists, we found that the observed Ca 2؉ oscillations were triggered by activation of D1 class dopamine receptors (DARs). We further demonstrated that activation of phospholipase C was required for induction of dopamine- Dopamine is an important transmitter and neuromodulator in the brain. The cellular mechanisms by which dopamine affects neuronal function are only beginning to be elucidated (1, 2). Striatal medium spiny neurons (MSN) 1 express multiple subtypes of dopamine receptors (DARs) (3-5). On the basis of their molecular structure and pharmacological properties, DARs are divided into the D1 class (D1R and D5R) and D2 class (D2R, D3R, and D4R) (6). D1 class DARs are coupled to G s/olf , activation of adenylyl cyclase, and cAMP production (3). Activation of D2 class DARs has dual effects of inhibiting cAMP production (3) and activating phospholipase C␤ (PLC␤) (7). A putative D1 class DAR subtype coupled to PLC activation and phosphatidylinositol 4,5-diphosphate hydrolysis, but not to cAMP production, has been postulated (8 -10), but has not yet been isolated or cloned. Recently, a specific agonist for this receptor (SKF83959) was identified (11). The D1R-binding protein calcyon has been isolated by yeast two-hybrid methods (12). Association of D1/D5 receptors with calcyon enables coupling of D1/D5 receptors with G q/11 , resulting in PLC activation and inositol 1,4,5-trisphosphate (InsP 3 ) generation (12, 13). Cross-talk between cAMP and Ca 2ϩ signaling pathways plays an important role in dopaminergic signaling in the neostriatum (1). Activation of D1 class DARs enhances L-type Ca 2ϩ channel activity (14 -16) and currents via the ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (17) and the N-methyl-D-aspartic acid (NMDA) receptor (18,19). In contrast, activation of D2 class DARs reduces L-type Ca 2ϩ currents (7) and NMDA receptor activity (20). D1/D5 receptormediated facilitation of L-type Ca 2ϩ channels and AMPA and NMDA receptors results from increased phosphorylation of these channels by protein kinase A (PKA) (16, 21) and decreased dephosphorylation of these channels by protein phosphatase-1 (PP1) (17,22,23). DARPP-32 (dopamine-and cAMPregulated phosphoprotein of M r 32,000) (24, 25) is partly responsible for inhibition of PP1 activity following activation of D1/D5 receptors (26). DARPP-32 phosphorylated by PKA at a single threonine residue (Thr-34) is transformed into a potent inhibitor of PP1, which in turn regulates the phosphorylation state of many neurotransmitter receptors and voltage-gated ion channels (1).The type 1 inos...

show abstract

“…D 1 and D 5 are classified as D 1 -like receptors that stimulate adenylyl cyclase. In some cases, D 1 -like receptors may activate the phosphoinositide pathway (Friedman et al, 1997). D 2 , D 3 , and D 4 are classified as D 2 -like receptors that inhibit adenylyl cyclase.…”

Section: Dopamine Receptors In the Striatummentioning

confidence: 99%

Cholinergic interneuron characteristics and nicotinic properties in the striatum

2002

View full text Add to dashboard Cite

ABSTRACT:The neostriatum (dorsal striatum) is composed of the caudate and putamen. The ventral striatum is the ventral conjunction of the caudate and putamen that merges into and includes the nucleus accumbens and striatal portions of the olfactory tubercle. About 2% of the striatal neurons are cholinergic. Most cholinergic neurons in the central nervous system make diffuse projections that sparsely innervate relatively broad areas. In the striatum, however, the cholinergic neurons are interneurons that provide very dense local innervation. The cholinergic interneurons provide an ongoing acetylcholine (ACh) signal by firing action potentials tonically at about 5 Hz. A high concentration of acetylcholinesterase in the striatum rapidly terminates the ACh signal, and thereby minimizes desensitization of nicotinic acetylcholine receptors. Among the many muscarinic and nicotinic striatal mechanisms, the ongoing nicotinic activity potently enhances dopamine release. This process is among those in the striatum that link the two extensive and dense local arbors of the cholinergic interneurons and dopaminergic afferent fibers. During a conditioned motor task, cholinergic interneurons respond with a pause in their tonic firing. It is reasonable to hypothesize that this pause in the cholinergic activity alters action potential dependent dopamine release. The correlated response of these two broad and dense neurotransmitter systems helps to coordinate the output of the striatum, and is likely to be an important process in sensorimotor planning and learning.

show abstract

D1-like Dopaminergic Activation of Phosphoinositide Hydrolysis Is Independent of D1A Dopamine Receptors: Evidence from D1A Knockout Mice

Cited by 119 publications

References 12 publications

Quantitative Changes in Gαolf Protein Levels, but not D1 Receptor, Alter Specifically Acute Responses to Psychostimulants

Quantitative Changes in Gαolf Protein Levels, but not D1 Receptor, Alter Specifically Acute Responses to Psychostimulants

Dopamine Receptor-mediated Ca2+ Signaling in Striatal Medium Spiny Neurons

Cholinergic interneuron characteristics and nicotinic properties in the striatum

Contact Info

Product

Resources

About