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1. In unanaesthetized cats intraventricular injections of 2·5-10 µg nicotine produced blinking, narrowing of the palpebral fissures, retching, vomiting and asynchronous twitching of the ears. With larger doses (30-100 µg) the ear twitching was interrupted for a short time by laying back of the ears. Respiration first became laboured and deep, then rapid and shallow following which panting occurred. There was salivation, loud calling, micturition and defaecation. With still larger doses (300-1000 µg) there was torticollis, ataxia and blind charging sometimes followed by a clonic-tonic convulsion.

2. In cats anaesthetized with chloralose only some of these effects followed the intraventricular injection of nicotine, i.e. the ear response, respiratory changes and salivation. In addition, the pinna reflex was facilitated.

3. The ear response and the facilitation of the pinna reflex did not occur on perfusion of nicotine from a lateral ventricle to aqueduct. They result from an action on superficial structures in the cervical cord between C1 and C2. Applied to this region of the cord, nicotine produced the ear response within 10-60 sec, sometimes in concentrations as low as 1/100,000. Applied below C2, nicotine was ineffective.

4. Transecting the cord below C2 or cutting the dorsal and ventral roots of C1, C2 and C3 bilaterally did not affect the ear response produced by topical application or by intraventricular injection of nicotine. Transection of the cord above C1 abolished it.

5. Hexamethonium applied to the cervical cord between C1 and C2 inhibited the ear response and the facilitation of the pinna reflex whether produced by nicotine applied topically or injected intraventricularly.

6. The salivation and the respiratory changes produced by intraventricular injections of nicotine did not occur when nicotine was perfused from a lateral ventricle to the aqueduct. They result from an action of the nicotine on structures situated superficially in the brain stem. Nicotine had no sialogogue or respiratory effect when applied to the region of the cord at which it produced an ear response, but perfused through the subarachnoid space from interpeduncular fossa to cisterna magna or injected into the subarachnoid space alongside the brain stem, it produced these effects.

7. Hexamethonium perfused from interpeduncular fossa to cisterna magna inhibited the salivary secretion as well as the respiratory changes produced by nicotine similarly applied.

8. The efferent pathway for the salivation is parasympathetic since it no longer occurred after cutting the chorda-lingual nerve or after intravenous atropine.

9. Intravenous injections of nicotine also produced the ear response with facilitation of the pinna reflex, salivation and hyperventilation in the anaesthetized cat, but only the ear response and facilitation of the pinna reflex are central effects. The salivation and hyperventilation following intravenous injection are due to peripheral actions of nicotine.