Effect of Chlorpromazine on Septal Hyperactivity in the Rat

Abstract

The effect of chlorpromazine on the overt emotional activity of a hybrid strain of rats has been measured using an altered "emotionality rating scale." It has been found that 8 mg/kg of chlorpromazine intraperitoneally reduced the activity of rats with the septal nuclei destroyed, normal rats and control rats to the same emotional rating. This effect has been related to the postulated interrelationship of the septal area and the amygdaloid complex of nuclei. It seemed that impulses traversing the septal nuclei might be re-routed, so that destruction of the septal area need not necessarily cause total abolition of " septal-function."It has been suggested by Olds & Travis (1960) that chlorpromazine can inhibit a forebrain system, while leaving intact the functions of a midbrain system. This is compatible with the hypothesis that chlorpromazine activity is localized within the limbic lobe.A marked increase in emotional behaviour of animals after experimental ablation of the septal region of the forebrain has been reported (Brady & Nauta, 1953;King, 1958 ;King & Meyer, 1958). This hyper-emotionality is manifested by violent attack or flight reactions in response to previously neutral or innocuous stimuli. There is extreme muscular tension to a degree rarely, if ever, noted in the normal animal. Therefore, it is possible that the septal nuclei exert an important function in the "physiological tranquillization" of rats. Destruction of the septal nuclei results in the excited animal because the septum normally counterbalances a stimulatory area.Chlorpromazine has been shown to cause an activity shift in the opposite direction to that produced by septal destruction (Hunt, 1957). This author showed that, following chlorpromazine administration, both septal operated and unoperated rats were depressed.A study of the activity of chlorpromazine in rats with surgically destroyed septal nuclei has been made with a view to testing the hypothesis that the septal area "counterbalances " a stimulatory area of the brain. To locate the site of actions of chlorpromazine the extent of the effect of the drug on animals which were septally hyperactive was observed, and compared with the effect of chlorpromazine on normal rats and on control animals which had had a " sham " operation.

Effect of Psychotherapeutic Drugs on Hyperemotionality of Rats in Which the Olfactory Bulb Was Removed

“…On the basis of these findings, changes in emotional reactivity following lesions of the olfactory bulb and septal regions may be thought due to different mechanism in emotional unbalance (13). Hyperemotionality of the O.B.-rats was restored to normal by making other lesions in the amygdaloid regions of the brain (8).…”

Prolonged hyperreactivity of septal rats with intraventricular pretreatment of 6-hydroxydopamine

“…The results obtained by these recent studies are not consistent with the effects of chlorpromazine and haloperidol. These dopaminergic blockers have a transient depressant action on the septal rage syndrome (Raitt, Nelson, & Tye, 1961;Stark & Henderson, 1966). Marotta et al (1977) mentioned that the effects of these agents resembled the effects exerted by such nonspecific sedatives as methohexital.…”