Nicotine induced tremor and antidiuresis and brain nicotine levels in the rat

Injection of rats with 14C-labelled nicotine (3 mg/kg sc) resulted in tremor measured by an electronic device during the first minutes after the injection. The animals were decapitated immediately afterwards and tissue was removed for the measurement of nicotine and cotinine. In another set of experiments nicotine (2 mg/kg sc) was injected into alcohol anaesthetized rats, their urinary excretion was measured up to 40 min, and they were decapitated as above. Pretreatment with mecamylamine prevented nicotine-induced tremor and antidiuresis. It also lowered the brain and blood nicotine levels in tremor experiments but not in antidiuresis experiments. Restoration of tremor by arecoline did not modify the mecamylamine effects on the nicotine levels. The 2 mg/kg sc nicotine dose did not produce tremor although the brain nicotine levels at 10 min exceeded those measured at 2 min after 3 mg/kg of nicotine. It is concluded that the rate of receptor occupation is important in the nicotine tremor. Both tremor and antidiuresis correlate fairly well with brain nicotine levels whereas mecamylamine-nicotine antagonism is less clearly reflected in brain nicotine levels.