Muscarinic receptors acting at pre- and post-synaptic sites differentially regulate dopamine/DARPP-32 signaling in striatonigral and striatopallidal neurons

Kuroiwa, Mahomi; Hamada, Miho; Hieda, Eriko; Shuto, Takahide; Sotogaku, Naoki; Flajolet, Marc; Snyder, Gretchen L.; Hendrick, Joseph P.; Fienberg, Allen A.; Nishi, Akinori

doi:10.1016/j.neuropharm.2012.07.046

Cited by 19 publications

(12 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…p11 is highly expressed in NAc CINs ( Warner-Schmidt et al, 2012 ) and is involved in the regulation of ACh release ( Virk et al, 2016 ). In addition, ACh has been shown to stimulate dopamine release via activation of α4β2 nicotinic ACh receptors (nAChRs) ( Wonnacott et al, 2000 ; Hamada et al, 2004 ) and M5 muscarinic receptors (mAChRs) ( Bendor et al, 2010 ; Kuroiwa et al, 2012 ) at dopaminergic axon terminals. These observations suggest that p11 regulates mesolimbic dopamine release by regulating cholinergic signaling at dopaminergic axon terminals.…”

Section: Resultsmentioning

confidence: 99%

“…Our findings indicate that, in the NAc, activation of CINs and the subsequent release of ACh are required for dopamine responses to rewarding stimuli, and that p11 is essential for CIN activation in response to reward. It is likely that ACh released from CINs in a p11-dependent manner activates the dopamine release machinery via activation of α4β2 nAChRs ( Wonnacott et al, 2000 ; Hamada et al, 2004 ) and M5 muscarinic receptors ( Bendor et al, 2010 ; Kuroiwa et al, 2012 ) at dopaminergic axon terminals, leading to the enhancement of the increase in extracellular dopamine induced by cocaine, a dopamine reuptake inhibitor. Furthermore, p11-dependent activation of CINs and ACh release seems to be optimal to enhance the dopamine reward probability, because the inverted U-shape threshold model suggests that activation of CINs above a certain threshold reduces it ( Grasing, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

p11 in Cholinergic Interneurons of the Nucleus Accumbens Is Essential for Dopamine Responses to Rewarding Stimuli

Hanada

Kawahara

Ohnishi

et al. 2018

eNeuro

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

p11 in Cholinergic Interneurons of the Nucleus Accumbens Is Essential for Dopamine Responses to Rewarding Stimuli

Hanada

Kawahara

Ohnishi

et al. 2018

eNeuro

View full text Add to dashboard Cite

show abstract

“…Both receptors investigated here are coupled to G o/i signaling and are expressed in the brain circuits involved in schizophrenia, including the striatum, cortex, and hippocampus (Hersch et al 1994 ; Levey et al 1991 , 1995 ). The M 4 receptor regulates the activity of dopaminergic and/or acetylcholinergic neurons in the striatum and nucleus accumbens (Ince et al 1997 ; Jeon et al 2010 ; Dencker et al 2012 ; Nadal et al 2016 ; Pancani et al 2014 ; Bell et al 2013 ; Kuroiwa et al 2012 ). Similar action may exert mGlu 4 receptors (Pancani et al 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Mutual activation of glutamatergic mGlu4 and muscarinic M4 receptors reverses schizophrenia-related changes in rodents

et al. 2018

View full text Add to dashboard Cite

RationaleMetabotropic glutamate receptors and muscarinic M4 receptors have been proposed as novel targets for various brain disorders, including schizophrenia. Both receptors are coupled to Go/i proteins and are expressed in brain circuits that are important in schizophrenia. Therefore, their mutual activation may be an effective treatment and allow minimizing the doses of ligands required for optimal activity.ObjectivesIn the present studies, subactive doses of mGlu4 and M4 activators (LSP4-2022 and VU152100, respectively) were administered to investigate the mutual interaction between mGlu4 and M4 receptors in animal models of schizophrenia.MethodsThe behavioral tests used were MK-801-induced hyperactivity, (±)-2.5-dimethoxy-4-iodoamphetamine hydrochloride (DOI)-induced head twitches, the modified forced swim test, and MK-801-induced disruptions of social interactions and novel object recognition. DOI-induced spontaneous excitatory postsynaptic currents (sEPSCs) in brain slices and positron emission tomography (PET) in were used to establish the ability of these compounds to modulate the glutamatergic and dopaminergic systems. Rotarod was used to assess putative adverse effects.ResultsThe mutual administration of subactive doses of LSP4-2022 and VU152100 exerted similar antipsychotic-like efficacy in animals as observed for active doses of both compounds, indicating their additive actions. VU152100 inhibited the DOI-induced frequency (but not amplitude) of sEPSCs in the frontal cortex, confirming presynaptic regulation of glutamate release. Both compounds reversed amphetamine-induced decrease in D2 receptor levels in the striatum, as measured with [18F]fallypride. The compounds did not induce any motor impartments when measured in rotarod test.ConclusionsBased on our results, the simultaneous activation of M4 and mGlu4 receptors is beneficial in reversing MK-801- and amphetamine-induced schizophrenia-related changes in animals.Electronic supplementary materialThe online version of this article (10.1007/s00213-018-4980-y) contains supplementary material, which is available to authorized users.

show abstract

“…The muscarinic antagonist scopolamine potentiated behavioral effects of systemic or intrastriatal D 1 , but not D 2 agonist administration in rats (Bordi and Meller 1989; Morelli et al 1993). In mouse striatal slices, the non-selective muscarinic agonist oxotremorine increased DARP-32 phosphorylation in D 1 -expressing striatonigral but not in D 2 -expressing striatopallidal medium spiny neurons (Kuroiwa et al 2012). As opposed to the D 1 antagonist effects, D 1 agonist effects on locomotor activity were exaggerated in M 4 −/− mice relative to wild-type (Gomeza et al 1999a).…”

Section: Discussionmentioning

confidence: 99%

Effects of dopamine D1-like and D2-like antagonists on cocaine discrimination in muscarinic receptor knockout mice

Thomsen

Caine

2016

European Journal of Pharmacology

View full text Add to dashboard Cite

Muscarinic and dopamine brain systems interact intimately, and muscarinic receptor ligands, like dopamine ligands, can modulate the reinforcing and discriminative stimulus (SD) effects of cocaine. To enlighten the dopamine/muscarinic interactions as they pertain to the SD effects of cocaine, we evaluated whether muscarinic M1, M2 or M4 receptors are necessary for dopamine D1 and/or D2 antagonist mediated modulation of the SD effects of cocaine. Knockout mice lacking M1, M2, or M4 receptors, as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10 mg/kg cocaine from saline in a food-reinforced drug discrimination procedure. Effects of pretreatments with the dopamine D1 antagonist SCH 23390 and the dopamine D2 antagonist eticlopride were evaluated. In intact mice, both SCH 23390 and eticlopride attenuated the cocaine discriminative stimulus effect, as expected. SCH 23390 similarly attenuated the cocaine discriminative stimulus effect in M1 knockout mice, but not in mice lacking M2 or M4 receptors. The effects of eticlopride were comparable in each knockout strain. These findings demonstrate differences in the way that D1 and D2 antagonists modulate the SD effects of cocaine, D1 modulation being at least partially dependent upon activity at the inhibitory M2/M4 muscarinic subtypes, while D2 modulation appeared independent of these systems.

show abstract

Muscarinic receptors acting at pre- and post-synaptic sites differentially regulate dopamine/DARPP-32 signaling in striatonigral and striatopallidal neurons

Cited by 19 publications

References 55 publications

p11 in Cholinergic Interneurons of the Nucleus Accumbens Is Essential for Dopamine Responses to Rewarding Stimuli

p11 in Cholinergic Interneurons of the Nucleus Accumbens Is Essential for Dopamine Responses to Rewarding Stimuli

Mutual activation of glutamatergic mGlu4 and muscarinic M4 receptors reverses schizophrenia-related changes in rodents

Effects of dopamine D1-like and D2-like antagonists on cocaine discrimination in muscarinic receptor knockout mice

Contact Info

Product

Resources

About