| abstract |
The invention features a method of screening for an agent that inhibits intracellular phosphodiesterase 10A activity, comprising administering an agent to striatal medium spiny neurons and submaximally activating adenylate cyclase, administering an agent to striatal medium spiny neurons and submaximally activating guanylate cyclase, measuring cAMP generation and cGMP generation in the cells, and calculating the cAMP EC200 and the cGMP EC200, wherein the agent is identified as a PDE10A inhibitor if the ratio of cAMP EC200/ cGMP EC200 is comparable to the ratio produced by administration of papaverine under the same assay conditions. Also featured are rat PDE10A polynucleotide and polypeptide sequences. |