EFFECTS OF SELECTIVE ADENOSINE A(1) AND A(2) RECEPTOR AGONISTS AND ANTAGONISTS ON LOCAL-RATES OF ENERGY-METABOLISM IN THE RAT-BRAIN

The quantitative [C-14]2-deoxyglucose autoradiographic technique was a pplied to the measurement of the cerebral metabolic effects of adenosi ne A(1) and A(2) receptor agonists and antagonists in adult rats. The adenosine A(1) receptor agonist and antagonist, 2-chloro-N-6-cyclopent yladenosine (CCPA) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as w ell as the adenosine A(2) receptor agonist, hyl)phenylethylamino]-5'-e thylcarboxamidoadenosine (CGS 21680), were injected at the dose of 0.0 1 mg/kg. The adenosine A(2) receptor antagonist, 3,7-dimethyl-1-propar gylxanthine (DMPX) was injected at the dose of 0.3 mg/kg. These doses were chosen in accordance with the known affinity of the drugs for the ir respective receptor and to avoid peripheral effects. The adenosine A(1) receptor agonist, CCPA, induced decreases in glucose utilization in three brain areas, the globus pallidus and two hypothalamic nuclei. The adenosine A(2) receptor agonist, CGS 21680, induced more general depressant effects on energy metabolism which were significant in 17 b rain areas, such as cerebral cortex, hippocampal and white matter regi ons plus motor and limbic structures. The adenosine A(2) receptor anta gonist, DMPX, decreased glucose utilization in the globus pallidus whi le increasing energy metabolism in the cochlear nucleus. The adenosine A(1) receptor antagonist, DPCPX, depressed glucose utilization in the globus pallidus and dentate gyrus, and increased rates of energy meta bolism in six regions, mainly hypothalamic, thalamic areas and in the cochlear nucleus. There was a mismatch between cerebral metabolic cons equences of adenosine A(1) and A(2) receptor agonists and the localiza tion of corresponding adenosine receptors. The metabolic effects of th e adenosine A(2) receptor agonist and antagonist were consistent with the known involvement of that type of receptor in the control of locom otion and its effects on neuronal firing in the hippocampus and cerebr al cortex. The effects of the adenosine A(1) receptor agonist were ver y discrete and mostly related to the transient decrease in blood press ure induced by the drug. The increases in glucose utilization induced in limbic regions by the adenosine A(1) receptor antagonist are probab ly linked to the regulation by adenosine of arousal and cardiorespirat ory function. These results are in good agreement with the neuroregula tory function of the adenosine system as previously shown by other met hods.