Evidence map›Paper›PMID 38987488›Full record

ArticleMolecular neurobiology2025

CREB-Binding Protein Regulates Cocaine- and Amphetamine-Regulated Transcript Peptide Expression in the Lateral Hypothalamus: Implication in Reward and Reinforcement.

Namrata Pawar, Biru B Dudhabhate, Vaishnavi Borade, Dipak K Sahare, Yogesh V Bhute, Nishikant K Subhedar, Dadasaheb M Kokare, Amul J Sakharkar

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Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Namrata PawarDepartment of Biotechnology, Savitribai Phule Pune University, Pune, 411 007, India.
Biru B DudhabhateDepartment of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, 440 033, India.
Vaishnavi BoradeDepartment of Biotechnology, Savitribai Phule Pune University, Pune, 411 007, India.
Dipak K SahareDepartment of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, 440 033, India.
Yogesh V BhuteDepartment of Zoology, DRB Sindhu Mahavidyalaya, Nagpur, 440 017, India.
Nishikant K SubhedarIndian Institute of Science Education and Research (IISER), Pune, 411 008, India.
Dadasaheb M KokareDepartment of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, 440 033, India. kokaredada@yahoo.com.
Amul J SakharkarDepartment of Biotechnology, Savitribai Phule Pune University, Pune, 411 007, India. amul.sakharkar@unipune.ac.in.

Funding

Science and Engineering Research Board CRG/2020/004971
6 · The paper itself

Abstract

Neuropeptide cocaine- and amphetamine-regulated transcript peptide (CARTp) is known to play an important role in reward processing. The rats conditioned to intra-cranial self-stimulation (ICSS) showed massive upregulation of CART protein and mRNA in the vicinity of the electrode implanted to deliver the electric current directly at the lateral hypothalamus (LH)-medial forebrain bundle (MFB) area. However, the underlying mechanisms leading to the upregulation of CART in ICSS animals remain elusive. We tested the putative role of CREB-binding protein (CBP), an epigenetic enzyme with intrinsic histone acetyltransferase (HAT) activity, in regulating CART expression during ICSS. An electrode was implanted in LH-MFB and the rats were conditioned to self-stimulation in an operant chamber. CBP siRNA was delivered ipsilaterally in the LH-MFB to knock-down CBP and the effects on lever press activity were monitored. While ICSS-conditioned rats showed distinct increase in CART, CBP and pCREB levels, enhanced CBP binding and histone acetylation (H3K9ac) were noticed on the CART promoter in chromatin immunoprecipitation assay. Direct infusion of CBP siRNA in the LH-MFB lowered lever press activity, CBP levels, histone acetylation at the CART promoter, and CART mRNA and peptide expression. Co-infusion of CARTp in LH-MFB rescued the waning effects of CBP siRNA on self-stimulation. We suggest that CBP-mediated histone acetylation may play a causal role in CART expression in LH, which in turn may drive the positive reinforcement of lever press activity.

Indexed as

CREB-Binding ProteinHypothalamic Area, LateralNerve Tissue ProteinsReinforcement, PsychologyRewardAcetylationAnimalsCocaine- and Amphetamine-Regulated Transcript ProteinConditioning, OperantGene Expression RegulationHistonesMalePromoter Regions, GeneticRatsRats, Sprague-DawleyRNA, MessengerCocaine- and Amphetamine-Regulated Transcript ProteinCREB-Binding ProteinHistonesNerve Tissue ProteinsRNA, MessengerRNA, Small InterferingCocaine- and amphetamine-regulated transcript peptideCREB-binding proteinHistone acetylationLateral hypothalamusReward and reinforcement

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.