Abstract: Methods for prophylactically treating a stress-induced affective disorder or stress-induced psychopathology in a subject are provided. Also provided are methods for inducing and/or enhancing stress resilience in a subject. In certain embodiments, an effective amount, of an antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptor, such as ketamine, or a pharmaceutically acceptable salt or derivative thereof, is administered to a subject prior to a stressor.

Abstract: Methods for prophylactically treating a stress-induced affective disorder or stress-induced psychopathology in a subject are provided. Also provided are methods for inducing and/or enhancing stress resilience in a subject. In certain embodiments, an effective amount, of an antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptor, such as ketamine, or a pharmaceutically acceptable salt or derivative thereof, is administered to a subject prior to a stressor.

Abstract: Disclosed is a FAST (Flexible Accelerated STOP TetO-knockin) system, an efficient method for manipulating gene expression in vivo to rapidly screen animal models of disease. This invention further discloses a single gene targeting event yielding 2 distinct knockin mice—STOP-tetO and tetO knockin—which permit generation of multiple strains with variable expression patterns: 1) knockout, 2) Cre-mediated rescue; 3) tTA-mediated misexpression; 4) tTA-mediated overexpression; and 5) tTS-mediated conditional knockout/knockdown. Using the FAST system, multiple gain- and loss-of-function strains can therefore be generated on a timescale not previously achievable. These strains can then be screened for clinically-relevant abnormalities. The flexibility and broad applicability of the FAST system is demonstrated by targeting several genes encoding proteins implicated in neuropsychiatric disorders: Mlc1, Neuroligin 3, the serotonin 1A receptor, and the serotonin 1B receptor.

Abstract: Disclosed is a FAST (Flexible Accelerated STOP TetO-knockin) system, an efficient method for manipulating gene expression in vivo to rapidly screen animal models of disease. This invention further discloses a single gene targeting event yielding 2 distinct knockin mice—STOP-tetO and tetO knockin—which permit generation of multiple strains with variable expression patterns: 1) knockout, 2) Cre-mediated rescue; 3) tTA-mediated misexpression; 4) tTA-mediated overexpression; and 5) tTS-mediated conditional knockout/knockdown. Using the FAST system, multiple gain- and loss-of-function strains can therefore be generated on a timescale not previously achievable. These strains can then be screened for clinically-relevant abnormalities. The flexibility and broad applicability of the FAST system is demonstrated by targeting several genes encoding proteins implicated in neuropsychiatric disorders: Mlc1, Neuroligin 3, the serotonin 1A receptor, and the serotonin 1B receptor.

Abstract: This invention provides a method for identifying a small molecule as an antidepressant, a method for identifying a small molecule as an anxiolytic, and a method for identifying a small molecule as able to increase dendritic arborization, decrease expression of an immaturity marker, increase expression of a maturity marker, or enhance artificial cerebrospinal fluid-type long-term potentiation in central nervous system. This invention also provides a transgenic mouse model for SSRI-non-responders.

Abstract: This invention provides a method for treating a subject afflicted with an anxiety disorder whose symptoms are exacerbated by the subject's exposure to a predetermined eliciting event, which method comprises administering to the subject a therapeutically effective amount of a protein synthesis inhibitor before, during the time, and/or after the subject intentionally recalls the eliciting event. Furthermore, this invention provides a method for inhibiting in a subject the onset of an anxiety disorder in response to an anxiety disorder-causing event. Finally, this invention provides a related article of manufacture.

Abstract: This invention provides methods for determining whether an agent, known to upregulate the sonic hedgehog pathway, increases brain progenitor cell division in a subject. Furthermore, this invention provides methods for treating anxiety, depression, a cognitive disorder or a neuro-degenerative disorder or inhibiting the onset of anxiety, depression or a cognitive disorder by administering to an afflicted subject a therapeutically or prophylactically effective amount of the agent known to upregulate the sonic hedgehog pathway. Finally, this invention provides methods for treating anxiety, depression, a cognitive disorder or a neuro-degenerative disorder or inhibiting the onset of anxiety, depression or a cognitive disorder by administering to an afflicted subject a therapeutically or prophylactically effective amount of Hh-Ag 1.1, Hh-Ag 1.2, Hh-Ag 1.3, or a derivative of Hh-Ag 1.1, Hh-Ag 1.2 or Hh-Ag 1.3.

Abstract: This invention provides a method for determining whether an agent reduces anxiety and/or depression in a depressed, non-human subject. This invention also provides methods for treating anxiety and depression in subjects afflicted with those disorders comprising administering a therapeutically effective amount of an anxiety-reducing or depression-reducing agent identified by the instant method.

Abstract: This invention provides methods for determining whether an agent increases brain progenitor cell division in a subject. Furthermore, this invention provides methods for treating anxiety, depression, a cognitive disorder or a neuro-degenerative disorder or inhibiting the onset of anxiety, depression or a cognitive disorder by administering to an afflicted subject a therapeutically or prophylactically effective amount of the agent. Finally, this invention provides methods for treating anxiety, depression, a cognitive disorder or a neuro-degenerative disorder or inhibiting the onset of anxiety, depression or a cognitive disorder by administering to an afflicted subject a therapeutically or prophylactically effective amount of Hh-Ag 1.1, Hh-Ag 1.2, Hh-Ag 1.3, or a derivative of Hh-Ag 1.1, Hh-Ag 1.2 or Hh-Ag 1.3.

Abstract: The present invention concerns novel polypeptides designated 5HT5a having serotonin receptor activity, genetic material permitting their expression, any recombinant cell expressing said polypeptides and uses thereof.