Antihistamine medications have been suggested to elicit clinical features of
restless legs syndrome. The available data are limited, particularly concerning periodic leg movements during sleep, which are common in
restless legs syndrome and involve bursts of tibialis anterior electromyogram. Here, we tested whether the occurrence of tibialis anterior electromyogram bursts during non-rapid eye movement sleep is altered in
histidine decarboxylase knockout mice with congenital
histamine deficiency compared with that in wild-type control mice. We implanted six
histidine decarboxylase knockout and nine wild-type mice to record neck muscle electromyogram, bilateral tibialis anterior electromyogram, and electroencephalogram during the rest (light) period. The
histidine decarboxylase knockout and wild-type mice did not differ significantly in terms of sleep architecture. In both
histidine decarboxylase knockout and wild-type mice, the distribution of intervals between tibialis anterior electromyogram bursts had a single peak for intervals < 10 s. The total occurrence rate of tibialis anterior electromyogram bursts during non-rapid eye movement sleep and the occurrence rate of the tibialis anterior electromyogram bursts separated by intervals < 10 s were significantly lower in
histidine decarboxylase knockout than in wild-type mice. These data do not support the hypothesis that preventing brain
histamine signalling may promote
restless legs syndrome. Rather, the data suggest that limb movements during sleep, including those separated by short intervals, are a manifestation of subcortical arousal requiring the integrity of brain
histamine signalling.