A direct method for determination of the time integral of corticosterone availability in interstitial fluid of rats

Abstract

A novel method for direct determination of the time integral of free corticosterone levels in interstitial fluid was used to measure corticosterone availability at rest and during free-operant shock-avoidance (SA) training in male rats. The method employs a subcutaneously implanted device to continuously accumulate the free hormone at a rate proportional to local concentration. The proportional rate of accumulation is maintained by providing mass-action corticosterone binding capacity within the device such that the device establishes a diffusion gradient for free corticosterone. The rate of uptake is limited so as to avoid disturbing equilibrium between free and bound hormone in the environment of the device. Corticosterone accumulation increased to 3× baseline during SA and was dexamethasone suppressible. These findings demonstrate the utility of a method uniquely combining specific measurement of free hormone with time integration to yield estimates of hormone availability during behavioral performance by an untethered subject. The method is suggested to be applicable to measurement of an extremely wide variety of drugs and hormones, under generally nonconstraining conditions.