In Vivo Measurement of Extracellular Cyclic AMP in the Brain: Use in Studies of β‐Adrenoceptor Function in Nonanesthetized Rats

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Abstract
Microdialysis measurement of extracellular cyclic AMP (cAMP) in the cerebral cortex of conscious rats was evaluated as a method for assessing central β‐adrenoceptor function in vivo. Extracellular levels of the nucleotide were found to average 3 pmol/ml under baseline conditions. Local infusion of the β‐agonists norepinephrine (NE) and isoproterenol produced rapid (3 min) and marked (three‐ to sevenfold) dose‐dependent increases in extracellular cAMP. which were potentiated by the phosphodiesterase inhibitor rolipram, and blocked by the β‐antagonist timolol. Responses to both catecholamines underwent rapid desensitization (6–9 min) and recovered within several hours. Time‐course studies revealed that the baseline cAMP level underwent a gradual increase and then a decrease over the course of a single 8‐h run, and peaked at 24 h postimplantation. Responses to NE were stable for the first 24 h after implantation, then increased at 48 and 120 h. The causes of the latter changes may include reactions to novelty, local inflammatory responses, and/or reactions of adjacent glial cells to implantation. Overall, the results indicate that the microdialysiscAMP method can be extended to nonanesthetized animals and may be a useful tool for studying neurotransmission at central adenylate cyclase‐coupled membrane receptors during various behavioral states.