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Elucidating Ih Biophysical Epigenetic Modifications in VTA Dopaminergic Neurons after Contingent and Non-Contingent Cocaine Administration

Award Number: R16GM145475
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT The ventral tegmental area (VTA) is a key CNS region involved in the reward and reinforcement of natural substances and drugs, such as cocaine. Hyperpolarization-activated cation current (Ih) is a key participant in the fundamental intrinsic properties of dopaminergic (DA) neurons of the VTA. The ion channels that carry Ih are comprised of HCN subunits, predominantly the HCN2 in the VTA. Alteration of Ih due to drug exposure has been shown after cocaine sensitization (CS). This change in Ih may be a common physiological mechanism in central reward/reinforcement pathways that contributes to addiction. Epigenetic mechanisms like histone deacetylation are responsible for some crucial neuronal changes that occur following chronic drug administration. This project will study the epigenetic regulation of the Ih function during the development of CS and on the Intermittent access self-administration (IntA) model. The IntA in our opinion better simulates human drug consumption. The specific aims will include: 1) To investigate the VTA epigenomic profile after CS, IntA and Histone Deacetylase inhibitor (HDACi); 2) Electrophysiological examination of Ih in VTA DA neurons after CS, IntA and HDACi; 3) To measure changes in HCN2 subunits in the VTA after CS, IntA and HDACi; 4) To investigate if in vivo shRNA targeting HDAC2 alters the development of CS, IntA and Ih properties of VTA DA neurons. Examination of cocaine-induced epigenetic changes in the VTA can provide key information about neuroadaptations that occur during the development of addiction. The reversal of these epigenetic modifications by histone deacetylase inhibition might provide possible avenues for therapeutic pharmacological intervention.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $141,272 )
2024	2024	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	B622 MAIN BUILDING FLR 6	SAN JUAN	PR	00935	SAN JUAN	USA	Biomedical Research and Research Training	000	3	6/24/2024	NON-COMPETING CONTINUATION	$141,272
														Subtotal = $141,272

Issue Date FY: 2023 ( Subtotal = $224,690 )
2023	2023	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	B622 MAIN BUILDING FLR 6	SAN JUAN	PR	00935	SAN JUAN	USA	Biomedical Research and Research Training	001	2	7/5/2023	SUPPLEMENT FOR EXPANSION	$81,608
2023	2023	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	B622 MAIN BUILDING FLR 6	SAN JUAN	PR	00935	SAN JUAN	USA	Biomedical Research and Research Training	000	2	5/31/2023	NON-COMPETING CONTINUATION	$143,082
														Subtotal = $224,690

Issue Date FY: 2022 ( Subtotal = $140,145 )
2022	2022	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Biomedical Research and Research Training	000	1	7/13/2022	NEW	$140,145
														Subtotal = $140,145

Grand Total All Awards = $506,107

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Elucidating Ih Biophysical Epigenetic Modifications in VTA Dopaminergic Neurons after Contingent and Non-Contingent Cocaine Administration

Award Number: R16GM145475

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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