Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Experiments were performed on the role of ascending cholinergic and serotonergic electrocortical activating systems and their role in normal physiology and behavior. In urethane-anesthetized rats, electrocortical activation could be obtained by electrical stimulation of the amygdala, the dorsal raphe, the locus coeruleus area, the superior colliculus, and the orbitofrontal cortex. Activation elicited from the amygdala, the locus coeruleus area, and most orbitofrontal sites was abolished by systemic administration of the cholinergic-muscarinic antagonists scopolamine or atropine. Activation elicited from the dorsal raphe or superior colliculus was largely resistant to anti-muscarinic treatment but was abolished by methiothepin, a serotonergic antagonist. Infusions of the local anesthetic lidocaine into the basal forebrain abolished activation elicited from the amygdala. Basal forebrain cells which increased their firing during cortical activation (putative cholinergic cortically-projecting cells) could be excited by single pulse stimulation of the amygdala or locus coeruleus area.;In unanesthetized rats treated with reserpine (a monoamine depletor) and scopolcunine, all cortical activation was abolished. Subsequent treatment with pargyline (a monoamine oxidase inhibitor that restores cerebral serotonin levels after reserpine treatment) restored normal activation. However, various serotonergic receptor agonists produced only partial or no activation in rats treated with reserpine and scopolamine.;Differences between the effects of serotonergic antagonists in freely moving and urethane-anesthetized rats suggest that urethane produces anti-serotonergic effects. This hypothesis was confirmed in experiments using rat aortic rings in an organ bath; urethane antagonized the effects of serotonin and strongly enhanced the action of a serotonergic antagonist without altering the action of a noradrenergic antagonist.;Behavioral experiments with p-chlorophenylalanine (an inhibitor of serotonin synthesis) and buspirone (an agonist at serotonin autoreceptors) were consistent with the hypothesis that ascending serotonergic pathways play a role in the generation of spontaneous locomotion.;Together, these results indicate that (a) ascending cholinergic and serotonergic pathways provide final common pathways for cortical activation through which other brain systems can act; (b) serotonergic activation is linked to certain types of motor activity; and (c) experiments on serotonergic transmission in anesthetized animals may produce results that are irrelevant to the unanesthetized state.



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