Haloperidol-induced immediate early genes in striatopallidal neurons requires the converging activation of cAMP/PKA/DARPP-32 and mTOR pathways
Onimus, O.; Valjent, E.; Fisone, G.; Gangarossa, G.
Show abstract
Antipsychotics share the common pharmacological feature of antagonizing the dopamine 2 receptor (D2R) which is abundant in the striatum and involved in both the therapeutic and side effects of this drugs class. Pharmacological blockade of striatal D2R, by disinhibiting the D2R-containing medium-size spiny neurons (MSNs), leads to a plethora of molecular, cellular and behavioral adaptations which are central in the action of antipsychotics. Here, we focused on the cell type-specific (D2R-MSNs) regulation of some striatal immediate early genes (IEGs), such as cFos, Arc and Zif268. Taking advantage of transgenic mouse models, pharmacological approaches and immunofluorescence analyses, we found that haloperidol-induced IEGs in the striatum required the synergistic activation of A2a (adenosine) and NMDA (glutamate) receptors. At the intracellular signaling level, we found that the PKA/DARPP-32 and mTOR pathways synergistically cooperate to control the induction of IEGs by haloperidol. By confirming and further expanding previous observations, our results provide novel insights into the regulatory mechanisms underlying the molecular/cellular action of antipsychotics in the striatum.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Arginase Inhibition Supports Survival and Differentiation of Neuronal Precursors in Adult Alzheimer's Disease Mice 93%
- Triac treatment prevents neurodevelopmental and locomotor impairments in thyroid hormone transporter Mct8/Oatp1c1 deficient mice 92%
- RTL4, a retrovirus-derived gene implicated in autism spectrum disorder, is a microglial gene that responds to noradrenaline in the postnatal brain 92%
Similar papers in this journal
- Experimental parkinsonism induced by tetanus toxin injected into basal ganglia 94%
- Cortical lipids containing choline mediate cannabinoid-induced cognitive improvement 92%
- Cross-pathway integration of cAMP signals through cGMP and calcium-regulated phosphodiesterases in mouse striatal cholinergic interneurons. 91%
Similar papers in this journal
- 17β-estradiol status alters NMDAR function and antipsychotic-like activity in female rats 93%
- LRRK2 mediates haloperidol-induced changes in indirect pathway striatal projection neurons 92%
- Ethanol's interaction with BK channel α subunit residue K361 does not mediate behavioral responses to alcohol in mice 92%
Similar papers in this journal
- Re-routing metabolism by the mitochondrial pyruvate carrier inhibitor MSDC-0160 attenuates neurodegeneration in a rat model of Parkinson's disease 95%
- Regulation of Brain Primary Cilia Length by MCH Signaling: Evidence from Pharmacological, Genetic, Optogenetic and Chemogenic Manipulations 92%
- A nanobody-based proximity ligation assay detects constitutive and stimulus-regulated native Arc/Arg3.1 oligomers in hippocampal neuronal dendrites 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.