Neuropharmacological profile of R 18 503-induced wet-shake behavior in the rat: Noradrenergic and opiate components

R 18 503 (α-(p-chlorophenyl)-β, β-dimethylimidazole-1-ethanol) 40 mg/kg IP produced a mean of 168 (SEM ± 4) wet shakes in the 35 min following its administration to 100 g male Wistar rats. No other behavioural abnormalities were seen at this dose. The wet-shakes were not caused by reduced body temperature. However, 20–30 min after R 18 503, body temperature was significantly elevated in comparison with saline treated controls. This supports a role for wet-shakes in thermogenesis in the rat, but suggests that R 18 503-induced wet-shakes are not adapted towards the maintenance temperature homeostasis. R 18 503-induced wet-shakes were potently antagonized by 5 narcotic analgesics, but not by aspirin-like drugs. A further 18 non-narcotic compounds including putative serotonin antagonists, neuroleptics and compounds thought to act on the α-adrenergic system, also antagonized R 18 503-induced wet-shakes. Spectral map analysis showed a close link between ED₅₀-values of the non-narcotic R 18 503 wet-shake antagonists and their ED₅₀'s to antagonize noradrenaline-induced lethality; this was further confirmed by a highly significant Spearman Rank correlation between the two test (r_s = 0.77, p<0.001). However, the spectral mapping and Spearman correlation analysis showed no relationship between antagonism of R 18 503-induced wet-shakes and antagonism of apomorphine-induced stereotypy, tryptamine-induced bilateral forepaw clonus, mescaline- induced head twitches, and 5-HT-induced contractions of rat caudal artery. It is postulated that R 18 503-induced wet-shakes result from an interaction between the opiate system and the α-adrenergic system.