Abstract: A transgenic rat containing in its genome a nucleotide sequence encoding a Ga subunit protein, which Ga protein subunit is uncoupled from regulation by Regulators of G-Protein Signaling (RGS) proteins, which Gx subunit protein is eventually the dominant-negative G188S mutant of Gax9, which nucleotide sequence is operatively associated with a neuron-specific expression control sequence, wherein the transgenic rat expresses the GA subunit protein in neural cells resulting in extended D-protein coupled receptor signaling mediated by the Ga subunit protein.

Abstract: A transgenic rat containing in its genome a nucleotide sequence encoding a Ga subunit protein, which Ga protein subunit is uncoupled from regulation by Regulators of G-Protein Signaling (RGS) proteins, which Gx subunit protein is eventually the dominant-negative G188S mutant of Gax9, which nucleotide sequence is operatively associated with a neuron-specific expression control sequence, wherein the transgenic rat expresses the GA subunit protein in neural cells resulting in extended D-protein coupled receptor signaling mediated by the Ga subunit protein.

Abstract: A transgenic rat containing in its genome a nucleotide sequence encoding a Ga subunit protein, which Ga protein subunit is uncoupled from regulation by Regulators of G-Protein Signaling (RGS) proteins, which Gx subunit protein is eventually the dominant-negative G188S mutant of Gax9, which nucleotide sequence is operatively associated with a neuron-specific expression control sequence, wherein the transgenic rat expresses the GA subunit protein in neural cells resulting in extended D-protein coupled receptor signaling mediated by the Ga subunit protein.

Abstract: This invention provides a transgenic mammal containing a defective beta 1 subunit (Kv&bgr;1) of a voltage sensitive potassium channel, where the Kv&bgr;1 subunit is unable to confer N-type inactivation of the K+ but retains the ability to co-associate with Kv1 family &agr;-subunits and thereby enhance channel surface expression. Preferably the Kv&bgr;1.1 gene encoding Kv&bgr;1 subunit has a mutation in all or a portion of codons 1-70 of its inactivation domain. The transgenic mammal is useful as a model for psychiatric and neurological disorders to identify anxiolytic compounds and pro-cognitive functions. The invention also provides for methods for screening and evaluating test compounds for their ability to modulate Kv&bgr;1.1 activity, specifically for inactivation of a potassium channel or for co-association with &agr;-subunits.

Abstract: Therapeutic combinations useful in the treatment or prevention of psychotic disorders, to pharmaceutical compositions containing said combinations, and to their use in the treatment or prophylaxis of prevention disorders are provided.