Increase in Rat Brain Tyrosine Hydroxylase Activity Produced by Electroconvulsive Shock

Abstract

Abstract.-A sustained increase in the turnover of norepinephrine coupled with an increased concentration of that amine has, in a previous study, been observed in the brains of rats exposed to electroconvulsive shock twice daily for one week. The phenomenon has been further examined by studying the effects of a similar regimen of electroconvulsive shock upon tyrosine hydroxylase in the brain, since that enzyme appears to be rate-limiting in norepinephrine synthesis. A small (15%) but significant increase in the whole brain enzyme activity was found in the electroshock-treated animals. A significant increase of tyrosine hydroxylase activity was found in the brainstem (24%) and cortex (20%) of such animals.Chronic electroconvulsive shock induces a sustained increase in the synthesis and utilization of norepinephrine in different parts of the rat central nervous system:' (a) brainstem and mesencephalon, (b) telencephalon and diencephalon, and (c) spinal cord. Since these changes in norepinephrine are observed 24 hours after the end of the electroconvulsive shock treatment, it was decided to examine the possibility that the acceleration of norepinephrine synthesis could be related to an increase in the activity of tyrosine hydroxylase which appears to be the rate-limiting enzyme in norepinephrine synthesis.Methods.-Male albino rats (Charles River Strain), approximately 275 gm in weight, were randomly divided into two groups: One of these groups was subjected to electroconvulsive shock for 7 days by the method employed previously;' the other was treated similarly, even to application of electrodes, except that the current was not turned on. The rats were decapitated 24 hr after the last period of electroconvulsive shock or "sham shock." The whole brain was quickly removed and frozen or dissected in the cold. The following regions were isolated: (a) brainstem and mesencephalon, (b) hypothalamus, (c) thalamus, (d) cortex, and (e) caudate nuclei. The tissues were then frozen and kept in dry ice until tyrosine hydroxylase was determined, between 36 hr and 3 days after decapitation. Freezing and storage for 3 days was found not to alter the activity of rat brain tyrosine hydroxylase.Partial purification and determination. of tyrosine hydroxylase: All the samples in experiment 1 (whole brain) and the samples corresponding to the same brain region (experimental and control) in experiment 2 were processed at one time, following a random order to minimize time effects. The frozen tissues were weighed and homogenized in 10 ml of ice-cold distilled water; larger amounts of tissue (cortex and the whole brain) were homogenized in 20 ml. All procedures were performed at 4VC unless otherwise stated.The homogenate was transferred to a polycarbonate centrifuge tube, balanced by the addition of water, and centrifuged at 100,000 X g for 1 hr. The supernatant was transferred to a 50-ml plastic centrifuge tube, and 7 ml (14 ml for the cortex and whole brain) of a saturated solution of ammoniuml sulfate were added while the mixture was bei...

Expression of c-Fos immunoreactivity in transmitter-characterized neurons after stress.

“…These results support many earlier studies of an involvement of catecholamines in stress reactions as measured with biochemical and histochemical (formaldehyde fluorescence) methods. Thus acute and/or chronic stress has been shown to affect norepinephrine (36)(37)(38)(39)(40)(41)(42)(43)(44)(45), epinephrine (46)(47)(48), and catecholamine-synthesizing enzymes (45)(46)(47)(48)(49)(50)(51). In agreement, both norepinephrine and epinephrine medullary neurons have been shown to contain the glucocorticoid receptor (52).…”

Electroconvulsive shock increases preproenkephalin messenger RNA abundance in rat hypothalamus.

“…Repetitive ECS treatment is known to produce a variety of delayed and persistent perturbations in central neurotransmitter systems, including increased norepinephrine content and turnover (27), decreased postsynaptic p-adrenergic receptor density (28), increased tyrosine hydroxylase protein and activity (29,30), increased serotonin content (27), and increased content of dynorphin [1][2][3][4][5][6][7][8] immunoreactivityt in specific brain regions. We expect that the elevated hypothalamic preproenkephalin mRNA abundance described here is only one of several ECS-produced alterations in specific mRNA levels.…”

Depletion of brain noradrenaline and dopamine by 6‐hydroxydopamine

“…Access to this mass was obtained through the lateral ventricle after hemisection of the whole brain. Tyrosine hydroxylase was isolated from these tissues according to the method of Musacchio, Julou, Kety & Glowinski (1969). Enzyme activity was determined by the method of Nagatsu, Levitt & Udenfriend (1964).…”