Effects of anti-histaminic and anti-cholinergic substances on human thermoregulation during cold provocation

The roles of histaminergic and cholinergic neuron systems in the regulation of body temperature have been studied almost exclusively in animals. Recently, we have found that motion sickness, i.e. a condition where hippocampal cholinergic mismatch signals induce a release of histamine in the vomiting centre, accelerates the decline in body temperature in men during exposure to cold. In the present study we measured the thermoregulatory effects of two substances commonly used against motion sickness, i.e. the histamine (H1) receptor blocker dimenhydrinate (DMH) and the muscarine receptor blocker scopolamine (SCOP). In three trials, control (CN), DMH and SCOP, 10 male subjects were immersed in 15 degrees C water for a maximum of 90 min. The trials were separated by a minimum of three days and their order was alternated between subjects. In all trials the subject received, in a double blind fashion, a transdermal patch (SCOP or placebo) 12-14 h before immersion and a tablet (DMH or placebo) 1h before immersion. Mean skin temperature, rectal temperature (T(rec)), the difference in temperature between the non-immersed right forearm and 3rd finger of the right hand (T(ff)), and oxygen uptake (VO(2)) were recorded. The fall in T(rec) was smaller in the DMH than in the CN and SCOP conditions. The recordings of T(ff) and VO(2) suggest that SCOP attenuates peripheral vasoconstriction while DMH increases shivering thermogenesis. Notably, thermal discomfort was reduced in the SCOP condition. Findings are thoroughly discussed in the context of animal studies on the neuropharmacology and neurophysiology of thermoregulation and motion sickness.