Neuropharmacological profile of R 18 503-induced wet-shake behavior in the rat: noradrenergic and opiate components.
R 18 503 (alpha-(p-chlorophenyl)-beta,beta-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 alpha-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 tests (rs = 0.77, p less than 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 alpha-adrenergic system.
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009294:Narcotics / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects; D012768:Shivering / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects
D007093:Imidazoles; D009294:Narcotics; D011941:Receptors, Adrenergic; D011957:Receptors, Opioid; D011985:Receptors, Serotonin; C034608:alpha-(4-chlorophenyl)-beta-dimethylimidazole-1-ethanol