Non-Human Animal Models of Depression and Methods of Use Thereof
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsKarl A. Deisseroth, Kay M. Tye, Melissa R. Warden
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Abstract
The disclosure provides non-human optogenetic animal models of depression. Specifically, non-human animals each expresses a light-responsive opsin in a neuron of the animal are provided. The animal models are useful for identifying agents and targets of therapeutic strategies for treatment of depression. Examples of using the non-human animals expressing light-responsive opsin including Halorhodopsin family of light-responsive chloride pumps and Channelrhodopsin family of light-responsive cation channel proteins are described.
Claims27
A method for identifying a candidate agent treating depression in an individual, comprising:
- contacting a rodent that expresses an active optogenetic inhibitor of neuronal activity in ventral tegmental area (VTA) dopaminergic neurons with a test agent, and
- determining the effect of the test agent on a behavior of the rodent in a depression assay,
- wherein reduction in a depressive behavior of the rodent contacted with the test agent, compared to the behavior of a control rodent that has not been contacted with the test agent, indicates that the test agent is a candidate agent for treating depression.
A transgenic rodent comprising dopaminergic neurons of the ventral tegmental area that express an optogenetic inhibitor of neuronal function.
A method for identifying a candidate agent for treating depression in an individual, comprising:
- contacting a rodent that expresses an active optogenetic activator of neuronal activity in ventral tegmental area (VTA) dopaminergic neurons with a test agent, and
- determining the effect of the test agent on a behavior of the rodent in a depression assay,
- wherein reduction in a depressive behavior of the rodent contacted with the test agent, compared to the behavior of a control rodent that has not been contacted with the test agent, indicates that the test agent is a candidate agent for treating depression.
A method for screening an agent for the ability to promote depression in an individual, the method comprising:
- contacting a rodent that expresses an active optogenetic activator of neuronal activity in ventral tegmental area (VTA) dopaminergic neurons with an agent, and
- determining the effect of the agent on the behavior of the rodent in a depression assay,
- wherein a depressive behavior of the rodent contacted with the agent, compared to the behavior of a control rodent that has not been contacted with the agent, indicates that the agent promotes depression.
A method for screening an agent for the ability to promote depression in an individual, the method comprising:
- contacting a rodent that expresses an active optogenetic activator of neuronal activity in medial prefrontal cortex (mPFC) excitatory neurons with an agent, and
- determining the effect of the agent on the behavior of the rodent in a depression assay,
- wherein a depressive behavior of the rodent contacted with the agent, compared to the behavior of a control rodent that has not been contacted with the agent, indicates that the agent promotes depression.
A method for identifying a candidate agent for treating an adverse psychological state in an individual, the method comprising:
- contacting a rodent that expresses an active optogenetic inhibitor of neuronal activity in ventral tegmental area (VTA) dopaminergic neurons with a test agent, and
- determining the effect of the test agent on a behavior of the rodent in a conditioned place aversion (CPA) test,
- wherein modulation in the CPA response behavior of the rodent contacted with the test agent, compared to the behavior of a control rodent that has not been contacted with the test agent, indicates that the test agent is a candidate agent for treating an adverse psychological state in an individual.
Dependencies are inferred from the claim text.