Use of microdialysis to measure brain noradrenergic receptor function in vivo.

The present studies were undertaken to explore the use of intracerebral microdialysis to measure brain adrenergic receptor activity in vivo using the efflux of cyclic adenosine monophosphate (cAMP) in the extracellular fluid as an index of receptor function. An initial study with brain slices showed that extracellular levels of cAMP were highly correlated with intracellular levels after noradrenergic receptor activation. Detectable levels of extracellular cAMP were obtained from microdialysis probes implanted in the frontal cortex. Stable levels (3.5 +/- 2.7 pmol/ml) were obtained between 1.5 and 7 h after implantation. Perfusion of probes with NE (10(-5) to 10(-3) M) led to dose-dependent increases in cAMP efflux. The response to NE was blocked by infusion of the beta-antagonist, timolol, indicating that it reflected beta-receptor activation. Similar responses were obtained at 2 and 24 h after implantation indicating that the responses were not affected by acute traumatic effects of implantation. The findings show that the microdialysis technique can be successfully applied to the in vivo study of central adrenoceptor function. This suggests that the in vivo measurement of second messengers by microdialysis will provide a valuable new neurochemical and neuropharmacological technique.