6-Hydroxydopa depletion of brain norepinephrine and the function of aggressive behavior.

A significant increase in shock-induced aggression occurs in the rat 4 days after an intraventricular injection of 90 micrograms of 6-hydroxydopa. Both fluorescent histology and biochemical assay demonstrate that brain norepinephrine is reduced by 90 micrograms of 6-hydroxydopa, while brain dopamine remains unaltered. This suggests that one form of aggressive behavior (shock-induced aggression) is modulated through a central noradrenergic system.

Proportional release of norepinephrine and dopamine- -hydroxylase from sympathetic nerves.

Dopamine-beta-hydroxylase(DBH), the enzyme that catalyzes the conversion of dopamine to norepinephrine, is localized in the vesicles containing catecholamine in sympathetic nerves. This enzyme is released with norepinephrine when the nerves to the guinea pig vas deferens are stimulated in vitro, and the amount of enzyme discharged increases as the length of stimulation periods increases. The amount of DBH released is proportional to the amount of norepinephrine released, and the ratio of norepinephrine to DBH discharged into the incubation medium is similar to that in the soluble portion of the contents of the synaptic vesicles from the vas deferens. These data are compatible with the release of the neurotransmitter norepinephrine and DBH from symnpathetic nerves by a process of exocytosis.

Rat fighting behavior: serum dopamine- -hydroxylase and hypothalamic tyrosine hydroxylase.

Male Sprague-Dawley rats were subjected to 4 weeks of daily periods of immobilization stress. One of two experimental groups was allowed 1 month of recovery. After 4 weeks of stress, there was a significant increase in shockinduced fighting, in the activity of serum dopamine-beta-hydroxylase, and in the activity of hypothalamic tyrosine hydroxylase. The concentration of hypothalamic norepinephrine was not decreased. After 4 weeks of recovery, only serum dopamine-betahydroxylase activity returned to normal; it therefore appears that longterm stress may increase central catecholamine synthesis. possibly resulting in a persistent increase in aggressive behavior.

Lithium increases serotonin release and decreases serotonin receptors in the hippocampus.

The effects of long-term lithium administration on pre- and postsynaptic processes involved in serotonergic neurotransmission were measured in rat hippocampus and cerebral cortex. Long-term lithium administration increased both basal and potassium chloride-stimulated release of endogenous serotonin from the hippocampus but not from the cortex. Serotonergic receptor binding was reduced in the hippocampus but not in the cortex. These results suggest a mechanism by which lithium may stabilize serotonin neurotransmission.

Modification of morphine-withdrawal syndrome in rats following transauricular electrostimulation: an experimental paradigm for auricular electroacupuncture.

The experimental paradigm reported here provides a useful animal model with which to further study the effects of regional electrostimulation and its possible relationship with electrical acupuncture. What similarities there may be between electrical acupuncture and the technique of regional electrocerebral stimulation used for production of electrosleep and electronarcosis in animals and man (Wageneder et al., 1966) remain to be elucidated. Further research studies, both clinical and basic, are clearly needed to answer some of the questions relating to the safety, efficacy, and possible mechanisms by which a technique such as electrical acupuncture may exert its effects.

Effects of vinblastine on catecholamine-biosynthetic enzymes in heart, sympathetic ganglion and adrenal glands of rats.

1. The effect of vinblastine on the activities of dopamine-beta-hydroxylase (DBH) in heart, superior cervical ganglion and adrenal glands of rats and tyrosine hydroxylase (TH) and phenylethanolamine-N-methyl transferase (PNMT) in adrenal glands was examined.2. In the superior cervical ganglion and heart, DBH activity decreased within hours, reached a minimum in 3 to 5 days and slowly returned towards normal over the next 2 weeks.3. There was an increase in the activities of TH, DBH and PNMT in adrenal glands which was prevented by adrenal denervation.4. When the same total dose of vinblastine was administered subdivided over a period of 5 days, enzyme activities in heart, superior cervical ganglion or adrenal glands remained unchanged.

Alterations of mouse adrenal medullary catecholamines and enzymes in response to attack: effect of pre- and post-treatment with phenobarbital.

Group-housed male C57BR/cdJ mice (victims) were exposed to attack for 10 min daily for up to 14 days by male Swiss-Webster mice, made aggressive by prolonged isolation. Their adrenal glands were analyzed for tyrosine hydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT) activities and for norepinephrine (NE) and epinephrine (EPI) concentrations. TH was increased to 41 per cent above control after two exposures and remained elevated through 14 exposures to attack. PNMT was increased to 29 per cent above control after 2 days and increased further to 50 per cent above control after 14 days of attack. Both NE and EPI increased to 88 per cent and 51 per cent above control, respectively, after 7 days. In victim mice recuperating after 1 week of daily stress, EPI levels and PNMT activities were back to normal after 4 days whereas NE levels and TH activities returned to normal only after 1 week. Phenobarbital (40 mg/kg, i.m.) was effective in preventing the biochemical changes when given 2 h prior to each daily attack but was ineffective when given immediately after each daily stress.

Release of alpha-melanocyte stimulating hormone into rat and human cerebrospinal fluid in vivo and from rat hypothalamus slices in vitro.

The release of alpha-melanocyte stimulating hormone (alpha-MSH) from central nervous system neurons was investigated and demonstrated in vivo and in vitro. alpha-MSH immunoreactivity in rat and human cerebrospinal fluid (CSF) is comprised of deacetylated alpha-MSH, alpha-MSH and the methionine sulfoxide forms of these peptides. The sulfoxides are formed artifactually upon extraction. alpha-MSH in rat CSF is unaffected by hypophysectomy but is markedly increased by electrical stimulation of the mesencephalic central gray. These data indicate that CSF alpha-MSH is primarily of neuronal origin, alpha-MSH is also released in a calcium dependent manner from hypothalamic slices in vitro. The fact that the release of alpha-MSH is stimulated by veratridine and inhibited by tetrodotoxin demonstrates the necessity for neuronal sodium influx for alpha-MSH release. The presence of an alpha-MSH neurosecretory process supports a neurotropic role for this peptide in the central nervous system.

Beta-adrenoceptors modulate noradrenaline release from axonal sprouts in cultured rat superior cervical ganglia.

Superior cervical ganglia of rats grown in organ culture were used to study the effect of beta-receptor stimulants and antagonists on 3H-noradrenaline release in response to stimulation by KC1 (75 mM). (--)-Isoprenaline 1X 10(-9)--1 X 10(-7) M) increased 20--25% the release of 3H-noradrenaline from cultured ganglia exposed to KC1. Isoprenaline did not modify either the spontaneous (non-calcium dependent) release of 3H-noradrenaline from cultured ganglia, or the KC1-stimulated release from fresh ganglia. The effect of (--)-isoprenaline was blocked by (--)-propranolol 5 X 10(-9) -- 1 X 10(-8) M and by butoxamine 10(-6) M, but not by (+)-propranolol (1 -- 5 X 10(-8) M), practolol (1 X 10(-8) -- 1 X 10(-6) M), or sotalol (1 X 10(-7) -- 1 X 10(-6) M). Isoprenaline induced augmentation of 3H-noradrenaline release and its antagonism by (--)-propranolol still occurred in the presence of DMI. It is suggested that presynaptic beta-receptors in sympathetic nerve terminals may be involved in a positive feedback of noradrenaline release.

Inhibition by halothane of release of norepinephrine, but not of dopamine-beta-hydroxylase, from guinea-pig vas deferens.

Halothane strikingly decreases spontaneous and electrically stimulated release of norepinephrine from the isolated guinea pig hypogastric nerve--vas deferens preparation. This depression of adrenergic discharge appears to be a direct action on the sympathetic nerve endings and may in part account for the cardiovascular depression seen during halothane administration. Although halothane depressed stimulation-induced release of norepinephrine, it did not proportionately diminish release of dopamine-beta-hydroxylase. Possible mechanisms of the dissociation between catecholamine and enzyme release are discussed.

Potassium evoked catecholamine release from the nucleus tractus solitarius in vitro.

The release of endogenous catecholamines (CA) from rat brain slices containing the nucleus tractus solitarius (NTS) was measured using a sensitive radioenzymatic assay. KCl (35 to 75 mM) induced a dose-related increase in norepinephrine (NE) release. Dopamine (DA) release was maximal with 50 mM KCl. An increase in epinephrine (E) release was only observed with 75 mM CKl. NE and E release was totally calcium-dependent whereas DA release was only partially calcium-dependent. Subsequent administrations of KCl released less CA. The calcium dependency of the KCl induced released of E, NE, and DA suggests a neurotransmitter function in the NTS for these CA. A difference in storage sites and/or mechanisms may be responsible for the observed differences in sensitivity to KCl and to extracellular calcium.

Catecholamines in discrete areas of the hypothalamus of obese and castrated male rats.

Levels of norepinephrine (NE) and dopamine (DA) were measured in eight discrete regions of the hypothalamus in three groups of male rats; genetically obese (fafa), non-obese (FaFa) and castrated non-obese (FaFa). DA levels showed no significant differences among the groups in any of the regions. NE levels in the paraventricular nucleus (PVN) were significantly lower in the obese and castrated animals than in the normal animals. In the median eminence (ME), NE levels were significantly decreased for the castrated group. None of the other regions sampled showed significant differences in NE levels.