Glucose Metabolism [14C-2-Deoxyglucose (14C-2-DG)]
14C-2-Deoxyglucose (14C-2-DG) Autoradiography – The 14C-2-DG autoradiographic method can be used for measuring glucose utilization as a function of neurogenic activity. This assay is useful for identifying brain regions activated by specific drug agents, and therefore, can act as a surrogate for functional MRI.
Measuring glucose consumption after acute i.p. administration of 20 mg/kg clozapine using 14C-2-DG autoradiography. Fifteen minutes after clozapine dosing, rats were i.v. tail vein injected with 25 μCi/kg of 14C-2-DG (sp. activity 275 mCi/mmol, Perkin Elmer). Rats were sacrificed 45 minutes post i.v. injection of 14C-2-DG. Six (6) 20 μM coronal sections were mounted on poly-lysine coated slides. Slides were loaded into the cassette of a Beta-imager 2000 (BioSpace Lab, France), and the images of the brain sections were acquired for 20 hours. Surface activity (cpm/mm2) was measured for specific brain regions using Beta vision + software (BioSpace Lab, France). The percent 14C-2-DG utilized was calculated as: [vehicle (cpm/mm2)–Clozapine (cpm/mm2)]/vehicle (cpm/mm2) X 100%. Analysis of rat brain striatal and thalamic areas reveals that Clozapine causes a 45-55% reduction in glucose metabolism. Widespread reduction in 2-DG by atypical antipsychotics, like Clozapine, is thought to result from blockade of dopamine, serotonin, muscarinic, and adrenergic neurotransmission.
