201. DARPP‐32 in the orchestration of responses to positive natural stimuli.
- Author
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Scheggi, Simona, De Montis, Maria Graziella, and Gambarana, Carla
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PHOSPHOPROTEINS ,ADENYLATE cyclase ,DOPAMINERGIC neurons ,CYCLIC-AMP-dependent protein kinase ,THREONINE - Abstract
Dopamine‐ and cAMP‐regulated phosphoprotein (Mr 32 kDa, DARPP‐32) is an integrator of multiple neuronal signals and plays a crucial role particularly in mediating the dopaminergic component of the systems involved in the evaluation of stimuli and the ensuing elaboration of complex behavioral responses (e.g., responses to reinforcers and stressors). Dopamine neurons can fire tonically or phasically in distinct timescales and in specific brain regions to code different behaviorally relevant information. Dopamine signaling is mediated mainly through the regulation of adenylyl cyclase activity, stimulated by D1‐like or inhibited by D2‐like receptors, respectively, that modulates cAMP‐dependent protein kinase (PKA) function. The activity of DARPP‐32 is finely regulated by its phosphorylation at multiple sites. Phosphorylation at the threonine (Thr) 34 residue by PKA converts DARPP‐32 into an inhibitor of protein phosphatase 1, while the phosphorylation at the Thr75 residue turns it into an inhibitor of PKA. Thus, DARPP‐32 is critically implicated in regulating striatal output in response to the convergent pathways that influence signaling of the cAMP/PKA pathway. This review summarizes some of the landmark and recent studies of DARPP‐32‐mediated signaling in the attempt to clarify the role played by DARPP‐32 in the response to rewarding natural stimuli. Particularly, the review deals with data derived from rodents studies and discusses the involvement of the cAMP/PKA/DARPP‐32 pathway in: 1) appetitive food‐sustained motivated behaviors, 2) motivated behaviors sustained by social reward, 3) sexual behavior, and 4) responses to environmental enrichment. Dopamine‐ and cAMP‐regulated phosphoprotein (Mr 32 kDa, DARPP‐32) is an integrator of multiple neuronal signals, in particular of dopaminergic and glutamatergic transmissions, and its activity is finely regulated by phosphorylation at multiple sites [threonine (Thr) 34 and 75; serine (Ser) 97 and 130]. This review discusses the role of DARPP‐32 in mediating biochemical, electrophysiological, transcriptional, and behavioral effects of dopamine. The evidences available on rodents, and some indirect evidence in humans, on the role played by DARPP‐32 in the integration of the responses to rewarding natural stimuli such as food, social and sexual interactions, and environmental enrichment are presented. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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