GROWTH HORMONE-RELEASING HORMONE ANTIBODIES SUPPRESS SLEEP AND PREVENT ENHANCEMENT OF SLEEP AFTER SLEEP-DEPRIVATION

Previous reports suggest that the hypothalamic growth hormone-releasing hormone (GHRH) promotes sleep, especially non-rapid-eye-movement sleep (NREMS). To evaluate the role of endogenous GHRH in sleep regulation, the effects of antibodies to rat GHRH (GHRH-ab) were studied on normal sleep, brain temperature (T(br)), and GH secretion in experiment I and on enhanced sleep after sleep deprivation in experiment II. In experiment I, affinity-purified GHRH-ab (50 and 200 mug) raised in goats and a control goat immunoglobulin G (IgG) preparation were injected intracerebroventricularly (icv) in rats 1 h before the onset of the light cycle, and sleep-wake activity and T(br) were recorded for the next 12 or 23 h. Both doses of GHRH-ab suppressed NREMS and REMS throughout the light cycle. Sleep durations at night were normal. Electroencephalographic (EEG) slow-wave activity, characterized by EEG slow-wave amplitudes, was reduced after GHRH-ab during both the light and the dark cycles. Plasma GH concentrations measured 6-12 h after injection of GHRH-ab (200 mug) were diminished. Both the control IgG and GHRH-ab elicited fever. In experiment II, the sleep-wake activity and T(br) of rats were recorded for 24 h in three experimental conditions: baseline with icv injection of IgG, 3-h sleep deprivation with icv IgG injection, and 3-h sleep deprivation with icv GHRH-ab (200 mug). After sleep deprivation (+IgG), a prompt increase in EEG slow-wave activity (power density analysis) and late increases in NREMS and REMS durations were found. Icv GHRH-ab blocked the increases in EEG slow-wave activity and sleep durations after sleep deprivation; in fact, sleep decreased below the baseline level. These results indicate that endogenous GHRH contributes to normal sleep regulation. In addition, GHRH seems to be involved in the mechanism of the enhanced recovery sleep after sleep deprivation.