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

Abstract

Microdialysis measurement of extracellular cyclic AMP (cAMP) in the cerebral cortex of conscious rats was evaluated as a method for assessing central .beta.-adrenoceptor function in vivo. Extracellular levels of the nucleotide were found to average 3 pmol/ml under baseline conditions. Local infusion of the .beta.-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 .beta.-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 microdialysis-cAMP 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.