MUSCARINIC ANTAGONISTS ARE ANXIOGENIC IN RATS TESTED IN THE BLACK-WHITE BOX

Central cholinergic (ACh) projections have been shown to modulate stre ss-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis and are integral to the expression of electrophysiological correlates of arousal, namely hippocampal theta rhythm. The degree to which thes e actions of ACh are behaviorally relevant has received comparatively less attention, and we sought to investigate if manipulations of ACh s ystems might also affect behaviors related to stress and arousal. We c hose to examine indices of anxiety as revealed by changes in behavior elicited by the black-white box test, a relatively novel and recently validated model of rodent anxiety. Groups of rats were injected with e ither scopolamine hydrobromide (SCOP; 0, 0.05, and 0.10 mg/kg IP) or t he peripherally acting scopolamine methyl bromide (methyl-SCOP; 0, 0.0 5, and 0.10 mg/kg IP) to compare and contrast the effects of central a nd peripheral ACh blockade on measures of anxiety. SCOP pretreatment s ignificantly lowered latencies for rats to escape from the white to bl ack compartment, while methyl-SCOP elevated latencies to reenter the w hite chamber from the black. Both drugs increased the amount of time r ats spent in the black compartment and also suppressed exploration as revealed by decreased episodes of intercompartmental locomotion. Neith er drug deleteriously affected locomotor activity, however; in fact, S COP significantly increased locomotion in the white chamber. In the ab sence of motor disturbances to account for any group differences, we c ontend that both central and peripheral ACh blockade may affect measur es of anxiety, perhaps by directly or indirectly affecting HPA activit y. Central ACh systems may underlie sensory filtering whereby irreleva nt stimuli are excluded from sensory processing. Antagonism of ACh tra nsmission may render an animal incapable of correctly processing senso ry information leading to hyperresponsiveness, which can manifest itse lf as enhanced anxiety and fear.