Sex differences in mouse behavior following pyrilamine treatment: role of histamine 1 receptors in arousal

Abstract

Arousal, the activation of brain and behavior, is a fundamental component of behavior. While sex differences in behavior are pervasive, it is unknown whether they could be due to an underlying dimorphism in arousal mechanisms. Because histamine (HA) acting through histamine 1 (H1) receptors is one essential component of arousal neural circuitry, the aim of the current experiment was to measure sex differences in behavioral arousal following treatment with the H1 receptor antagonist, pyrilamine (PYRL). Castrated male and ovariectomized female Swiss–Webster mice were treated subcutaneously with either 15 or 35 mg/kg of PYRL. The effect of drug treatment was determined in an array of behaviors: sensory responsiveness, running wheel activity, and fearfulness. Surprisingly, the lower dose of PYRL increased some aspects of arousal, sensory responsiveness, and anxiety-like behavior, while the higher dose of PYRL resulted in decreases in arousal across tests, indicating that antagonism of histamine receptors does not have a linear relationship with arousal. Females were more sensitive to the arousal-reducing effects of PYRL than males in sensory and running wheel tasks but not in tests of emotion. In conclusion, antagonism of H1 receptors can alter arousal in a sex-dependent manner, independent of circulating gonadal steroids, in mice.