Locomotor activity after nicotine infusions into the fourth ventricle of rats

Microinjections of nicotine into the fourth ventricle of rats were reported previously to produce a characteristic prostration syndrome; similar microinjections have been investigated for effects on locomotor activity. It was confirmed that nicotine (4 micrograms) administered into the fourth ventricle of rats produced prostration which was also manifested on a second challenge with the drug. Increasing doses of nicotine produced increasing magnitudes of prostration and dose-related decreases in locomotor activity. In rats pretreated with nicotine (0.4 mg/kg SC) for 10 days, no tolerance was seen to either the prostration response or the locomotor depression. Mecamylamine (1.0 mg/kg SC) completely prevented the prostration response produced by 4 micrograms of nicotine, but the locomotor depression was still evident. The locomotor changes following intraventricular administration of nicotine appeared to be different from the locomotor depression seen following systemic administration because the posture of the animals was different and the latter effects showed tolerance with repeated exposures to nicotine and were fully blocked by mecamylamine. These findings suggested that the prostration response and the locomotor depression were mediated by different mechanisms.