Very rapid turnover of dopamine in noradrenaline cell body regions

Abstract

The contents of dopamine, noradrenaline and their deaminated metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylethylene glycol (DOPEG) were determined in rats in two noradrenaline cell body regions, i.e., the superior cervical ganglion and the locus coeruleus, and in one dopamine cell body region, the substantia nigra. In the two noradrenaline cell body regions, the tyrosine hydroxylase inhibitor alpha-methyltyrosine rapidly lowered the contents of noradrenaline and DOPEG and it lowered the contents of dopamine and DOPAC even more rapidly. The dopamine-beta-hydroxylase inhibitor FLA-63 swiftly elevated the content of dopamine and it lowered the content of noradrenaline in the two noradrenaline regions, but it was ineffective in the substantia nigra. The monoamine oxidase inhibitor pargyline rapidly reduced the deaminated catechols and increased somewhat the contents of the two amines in the superior cervical ganglion and in the locus coeruleus. The alpha-methyltyrosine-induced disappearance of dopamine in the two noradrenaline cell body regions was markedly inhibited by FLA-63 and pargyline in combination, but not by only one of the two drugs. The results indicate that most of the dopamine in the superior cervical ganglion and in the locus coeruleus occurs in the cell body region of noradrenaline neurons, whereas only a minor part of the dopamine in the superior cervical ganglion is present in SIF cells. Axonal transport did not contribute to the disappearance of dopamine in the superior cervical ganglion. A high dose of reserpine reduced the contents of dopamine and noradrenaline in the superior cervical ganglion and in the locus coeruleus, indicating that most of the amines is present in storage granules.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of forebrain dopamine systems by phencyclidine and footshock stress: evidence for distinct mechanisms

“…In addition, the benzodiazepine receptor ligand FG 7142, which is reported to produce anxiety in man, has a selective action upon DA projections to the prefrontal cortex (Tam and Roth 1985), There is further evidence that conditioned stress or PCP increases dopamine metabolites in the VTA but not in the substantia nigra (Deutch et al 1985b). The neuronal origin of dopamine metabolites after footshock stress or drugs deserves consideration, since recent studies suggest that under certain circumstances dopamine metabolites may originate in noradrenergic neurons (Andtn et al 1985;Scheinin 1986). However prefrontal cortical dopamine was unaffected by lesions which completely destroyed the noradrenergic innervation of the prefrontal cortex (Bannon et al 1981).…”

“…Phencyclidine decreased both substance P and substance K in the ventral tegmental area. The results suggest that phencyclidine and footshock activate forebrain dopaminergic systems in part by separate mechanisms.Key words: Phencyclidine -Footshock stress -Prefrontal cortex -Substance P Substance K -Ventral tegmental area -Homovanillic acid Mild footshock stress to rats, exposure to the shock chamber as a conditioned stimulus, and a number of other stressors primarily activate the mesocortical dopamine (DA) systems as evidenced by an increase in mesocortical DA metabolites, (for a review, see Andtn et al 1985). At certain doses, phencyclidine (PCP), lysergic acid diethylamide (LSD), and zx9-tetrahydrocannabinol (THC) can also affect mesocortical pathways and in addition sometimes increase DA metabolites in the meso-limbic (rneso-olfactory tubercle) pathway as well (Bowers and Salomonsson 1982;Bowers and Hoffman 1984; Bowers and Hoffman 1986).…”

Studies of Catecholamine Metabolism in Schizophrenia/Psychosis-II

“…There is evidence that much of the HV A in plasma and urine is from metabolism of DA in noradrenergic neurons (Anden and Grabowska-Anden 1983;Anden et al 1985;Scheinin et al 1984;Scheinin 1986;Schei nin and Virtanen 1986;Kopin et al 1988a,b,c). In our haloperidol-treated patients, urinary HV A and MHPG changed in opposite directions over the fIrst several weeks.…”

Source and Physiological Significance of Plasma 3,4‐Dihydroxyphenylalanine in the Rat

“…Because plasma 3,4-dihydroxyphenylglycol (DHPG) is produced intraneuronally as a deaminated metabolite of NE (Goldstein et al, 1987) and 3,4-dihydroxyphenylacetic acid (DOPAC) is produced in noradrenergic nerves as a deaminated metabolite of dopamine (Anden and Grabowska-Anden, 1984;Anden et al, 1985), plasma concentrations of DHPG and DOPAC were examined simultaneously with those of DOPA and NE to relate changes in DOPA content to the intraneuronal deamination of NE and dopamine. Infusions of DOPA were camed out to determine the rate of DOPA clearance and thus the rate at which DOPA enters the bloodstream.…”

“…Conversion of DOPA to dopamine is catalyzed by aromatic amino acid decarboxylase, an enzyme widely dispersed throughout the body (Lovenberg et al, 1962). Dopamine is translocated from the axoplasm into storage vesicles and there converted to NE by dopamine-0-hydroxylase; however, a portion of the dopamine escapes vesicular uptake and is converted to DOPAC intraneuronally by MAO-A (Anden and Grabowska- Anden, 1984;Anden et al, 1985). This catabolic enzyme (inhibited by clorgyline) also maintains axoplasmic NE at low concentrations by metabolism of NE to DHPG.…”