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Molecular and Cellular Determinants of Tolerance to Second Generation Antipsychotics

NIMH - National Institute of Mental Health

open
OpenLast verified: 2026-06-20

About This Grant

Contact PD/PI: lewis, elinor PROJECT SUMMARY Second generation antipsychotics (SGAs) are widely used clinical tools for the treatment of severe mental illness. However, their utility is highly variable, and they take weeks to become effective. The mechanisms behind this time course are not understood. SGAs are thought of as antagonists at the D2 dopamine receptor. Yet our recent work suggests that some SGAs function as arrestin-biased agonists at the less-characterized D3 dopamine receptor (D3R). Activation of the arrestin-3 pathway leads to degradation of D3R, potentially altering response to these drugs over time. I have generated preliminary data that shows mice grow tolerant to preclinical measures of SGA activity after chronic treatment of an arrestin-biased SGA. I hypothesize that D3R neurons are the locus of tolerance to select SGAs, and this tolerance is driven by decreased D3R membrane expression caused by arrestin-3 recruitment to D3R. I will use in vivo optical methods to assess changes in D3-neuron activity after chronic SGA treatment. I will also measure behavioral tolerance to SGA treatment in transgenic mice with altered abilities to degrade D3Rs and compare D3R levels using saturation binding and PET scans. This project will reveal mechanisms of tolerance to select SGAs at gross anatomy, cell- type, and protein levels. Project Summary/Abstract Page 6

Grant Summary

Molecular and Cellular Determinants of Tolerance to Second Generation Antipsychotics is a NIMH - National Institute of Mental Health grant providing up to $34K for university, nonprofit, healthcare org. Applications are due 2027-10-31 (open). Check eligibility and apply with FindGrants.

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Focus Areas

health research

Eligibility

universitynonprofithealthcare org

How to Apply

Funding Range

Up to $34K

Deadline

2027-10-31

Complexity
Medium
  1. 1Confirm your organization is eligible for Molecular and Cellular Determinants of Tolerance to Second Generation Antipsychotics from NIMH - National Institute of Mental Health, checking organization type, location, and any population or project requirements.
  2. 2Gather the required documents and information, including your organization details, project plan, and budget figures.
  3. 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
  4. 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIMH - National Institute of Mental Health before the deadline.
This record is a past award, contract, or funder profile — useful for research, but not an open grant application. Check the original source for current opportunities from this funder.

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Molecular and Cellular Determinants of Tolerance to Second Generation Antipsychotics: Frequently Asked Questions

Who is eligible for the Molecular and Cellular Determinants of Tolerance to Second Generation Antipsychotics?

Molecular and Cellular Determinants of Tolerance to Second Generation Antipsychotics is offered by NIMH - National Institute of Mental Health and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.

How much funding does the Molecular and Cellular Determinants of Tolerance to Second Generation Antipsychotics provide?

Molecular and Cellular Determinants of Tolerance to Second Generation Antipsychotics provides up to $34K per award from NIMH - National Institute of Mental Health. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.

When is the Molecular and Cellular Determinants of Tolerance to Second Generation Antipsychotics deadline?

Applications for Molecular and Cellular Determinants of Tolerance to Second Generation Antipsychotics are due 2027-10-31 (open). Because deadlines can change, verify the date with the funder, NIMH - National Institute of Mental Health, and give yourself enough time to prepare a complete, competitive application before the close date.

How do you apply for the Molecular and Cellular Determinants of Tolerance to Second Generation Antipsychotics?

To apply for Molecular and Cellular Determinants of Tolerance to Second Generation Antipsychotics, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIMH - National Institute of Mental Health.