In vivo measurement of extracellular cyclic AMP in the brain: use in studies of beta-adrenoceptor function in nonanesthetized rats.
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.
Stone
E A
EA
Department of Psychiatry, New York University School of Medicine, New York.
John
S M
SM
D000758:Anesthesia; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002845:Chromatography; D000242:Cyclic AMP / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013997:Time Factors; D014520:Urethane
D010726:Phosphodiesterase Inhibitors; D011943:Receptors, Adrenergic, beta; D014520:Urethane; D000242:Cyclic AMP; D009638:Norepinephrine