Effects of corticosterone and 5α‐dihydrocorticosterone on brain excitability in the rat

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Abstract
The effects of corticosterone (B) and its reduced metabolite 5 ç‐dihydrocorticosterone (DHB) on CNS activity in the rat were examined. Two indices of brain excitability were evaluated: (1) amplitude of population responses (evoked potentials [EP] to sciatic nerve stimulation and 2) changes in the rate of firing of tonically discharging neuron‐both at pontine brainstem regions of the reticular formation. Experiments were carried out in adrenalectomized rats, and recordings were under urethane anesthesia. Steroids wer dissolved in a 4:1 saline:Cremophor‐El (Sigma) solution and does of 750 μg/0.5 ml were injected (IV). The effects of B on EPs were bidirectional. Increases (8 animals) and decreases (6 animals) of the amplitude responses in different animals were observed. In 4 animals, no changes were detected. In contrast, injection of DHB produced a consistent and significant reduction of brainstem sciatic evoked potentials in 10 of 12 animals tested; 2 animals did not respond to the steroid. At the neuronal level, the effects of the steroids were evaluated by the change they induced in the mean firing frequency (P < 0.01) measured during 5‐min intervals as determined by a one‐way analysis of variance and analysis with a test of multiple comparisons. Only cells that fired in stationary mode for 15 min before the steriod injection were stuided. A more consistent pattern of responses to B was observed at the single‐cell level. From 31 neurons that responded to the hormone, of 76 examined, 27 showed an increase in their firing rate and only 4 neurons showed a decrease. The increase in firing rate has an onset latency of 2–5 min (x = 3.5, SE 0.43) with a duration of 16–25 min (x = 17.5, SE 2.7). Of 69 neurons that were tested with DHB, 51 showed a significant decrease in their mean firing frequency. Onset latency of the effect was 2–8 min (x = 40.0, SE 1.21) and the duration of the induced changes was 16–40 min (x = 30.0, SE 3.47). Central interactions of DHB and B when sequentially administered were examined in 28 neurons. Of these, 21 responded to DHB administration with a significant decrease in their firing rates. In 11 of these neurons, injection of B, 5 min after DHB, was followed by a rapid (1–2 min) return of the neurons to baseline firing rates. In the other 10 neurons, injection of corticoterone altered neither the median return time (30 min) nor the slope of recovery to baseline firing levels. The results presented support the notion that nuclear saturated 3.20 oxygenated steroids are endowed with CNS depressant potency and support the contention that ring A‐reduced metabolites of ovarian and adrenal steroids may fulfill an important biologic role in modulating brain excitability. Further, the data support the concept that steroid interaction at nonnuclear site (S) may complement actions at the neclear level as well as the notion that a hormones may act at multiple loci in target cells.