Effects of scopolamine and its quaternary analogue in the murine elevated plus-maze test of anxiety

Abstract

Several lines of evidence suggest that muscarinic cholinergic receptors may play a role in fear/anxiety reactions in animals. In the present study, the behavioural effects of the muscarinic receptor antagonist scopolamine (0.125-1.0mg/kg) were examined in male mice exposed to the elevated plus-maze. In contrast to scopolamine methyl bromide, which was behaviourally inert under present test conditions, scopolamine hydrobromide produced behavioural changes indicative of enhanced anxiety. The effects included a reduction in percentage of open arm entries and a marked stimulation of risk assessment measures (i.e. stretched attend postures and closed arm returns), as well as more subjective signs of enhanced fear/anxiety such as vocalisation, struggling and escape-oriented behaviour. Although scopolamine also enhanced total arm entries, perhaps suggesting a general stimulant action, this effect was specific to the closed arms and was not accompanied by systematic increases in either rearing or head-dipping. Data are discussed in relation to the possible involvement of central muscarinic substrates in risk assessment behaviour in animals and hypervigilance states in humans.