Differential actions ofm and n cholinergic agonists on the brainstem activating system

The differential actions of i.v. arecoline and nicotine were determined on neocortical and limbic system EEG activation in acute rostral and caudal midbrain transected cats. All animals were prepared under diethyl ether anesthesia and after surgery, paralyzed with decamethonium and maintained on artificial respiration. The peripheral effects of these cholinergic agonists were reduced by methyl atropine (250 μg/kg ) and/or trimethidinium (1 mg/kg) pretreatment.

In the caudal midbrain transected preparation, nicotine (20–40 μg/kg) induced marked EEG activation in both the neocortex and hippocampus. After bilateral lesions of the midbrain reticular formation in the same preparation, EEG activation was not observed with nicotine in doses up to 100 μg/kg. The EEG effects of nicotine were blocked by atropine (1 mg/kg) and mecamylamine (1 mg/kg) but not trimethidinium (1 mg/kg). In the rostral midbrain transected preparation no EEG activation was noted with nicotine in doses up to 100 μg/kg. Sporadic sharp waves appeared in the hippocampus with the larger doses indicating a convulsant site of action above the level of transection.

Arecoline induced dissociation of the EEG in the hippocampus and neocortex in doses of 20–40 μg/kg in the rostral midbrain transected cat. Marked hippocampal slow “arousal” waves with no desynchronization of the neocortical EEG were seen. These effects of arecoline were blocked by atropine. In the caudal midbrain preparation, even after bilateral lesions of the midbrain reticular formation which blocked nicotine activation, arecoline (20–40 μg/kg) still induced hippocampal slow ‘arousal’ waves without neocortical desynchronization. With doses of 100 μg/kg of arecoline both neocortical and hippocampal EEG activation was noted.

It is concluded that the site of nicotine on the rostral forebrain activating system is located primarily in the midbrain reticular formation, whereas arecoline acts on the midbrain reticular formation as well as above the level of the mesencephalon.