Changes In Dopamine Concentrations Research Articles

Endogenous dopamine and cyclic events in the fish retina, I: HPLC assay of total content, release, and metabolic turnover during different light/dark cycles

In this study, we investigated the potency of dopamine for being an intrinsic signal for cyclic events in the fish retina. Dopaminergic activity was measured during different light/dark cycles, during continuous darkness, and during short-term light and dark adaptation within 1 h. During a 12-h light/12-h dark cycle, the total content of endogenous dopamine was high during the dark phase and low during the light phase. The potassium-induced release of endogenous dopamine followed a parallel time course. The concentration of the dopamine breakdown product 3,4-dihydroxyphenylacetic acid (DOPAC), which reflects the endogenous dopaminergic activity, was high during the light phase and low during the dark phase. Similar alterations occurred in accelerated 6-h light/6-h dark cycles, again indicating a strong coupling of dopaminergic activity with light. The cyclic alterations in the total endogenous dopamine content persisted during continuous darkness after an entrainment of the fish to a 12-h light/12-h dark cycle. Although the magnitude of the change was weaker, changes in dopamine content, potassium-induced dopamine release, and DOPAC were also measured during 1 h of light or dark adaptation. During a 1-h period of dark adaptation, the total content of dopamine and the potassium-induced release of endogenous dopamine increased, while DOPAC values decreased. These values changed in the opposite direction during 1 h of light adaptation. Our findings strongly suggest that dopamine is the intrinsic signal for light during both the light and dark phases and during short-term adaptation. Light seems to be the major trigger for dopaminergic activity within the fish retina.(ABSTRACT TRUNCATED AT 250 WORDS)

MPTP-induced parkinsonism: relative changes in dopamine concentration in subregions of substantia nigra, ventral tegmental area and retrorubral field of symptomatic and asymptomatic vervet monkeys

Dopamine (DA) and homovanillic acid (HVA) concentrations were measured in subregions of substantia nigra, ventral tegmental area and retrorubral field in vervet monkeys 1 to 2 months after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Identical MPTP treatment regimens produced animals with different degrees of parkinsonism. In asymptomatic monkeys, changes in DA and HVA concentrations in the midbrain DA regions were relatively small and involved central substantia nigra and dorsomedial ventral tegmental area. In contrast, changes in symptomatic monkeys were more severe and widespread, significantly affecting all examined subregions of substantia nigra (75% DA depletion), both dorsomedial and ventromedial ventral tegmental area and lateral, but not medial, retrorubral field. The data indicate that DA neurons in subregions of substantia nigra, ventral tegmental area and retrorubral field are not equally susceptible to MPTP toxicity. The pattern of MPTP-induced DA and HVA losses in the vervet monkey mesostriatal dopaminergic system may resemble postencephalitic Parkinson's disease more closely than idiopathic Parkinson's disease.

Acute changes in dopamine levels in rat adrenal glands after administration of dopamine receptor agonists and antagonists

The study was aimed at in vivo pharmacological identification of the possible dopamine (DA) receptor(s) involved in changes of the DA level in rat adrenal glands. Previous work in this laboratory has shown that the DA level is largely controlled by the rate of catecholamine synthesis. The rats were killed by decapitation after various periods of drug administration and the catecholamine content of adrenal glands and forebrain was measured by high-performance liquid chromatography with electrochemical detection. Administration of the DA D-1 + D-2 receptor agonist, apomorphine, induced a statistically significant increase in DA levels in the adrenal glands. The same effect was noted after administration of the DA D-2 receptor agonist, quinpirole. The DA D-2 receptor antagonist, raclopride, blocked the apomorphine-induced increase in adrenal DA levels but had no effect per se on these levels. The DA D-1 receptor agonist, SKF 38393, and the DA D-1 receptor antagonist, SCH 23390, did not have any effect on apomorphine-induced changes in DA content in the adrenals. The DA elevating effect of the DA D-2 receptor agonist, quinpirole, in the adrenals was completely blocked by the DA D-2 receptor antagonist, domperidone. This compound does not cross the blood-brain barrier readily and is thus supposed to act mainly on peripheral tissues. In support of this, the dose of domperidone used did not affect brain DOPAC levels. Our data, together with observations reported in the literature, indicate that the adrenal medulla contains DA receptors of the D-2 subtype, which are capable of controlling the DA level in rat adrenal glands.

3-Acetylpyridine-induced degeneration of the nigrostriatal dopamine system: An animal model of olivopontocerebellar atrophy-associated parkinsonism

The effects of 3-acetylpyridine (3-AP) administration to rats on the mesotelencephalic dopamine system were assessed. A single 3-AP injection resulted in biochemical and immunohistochemical evidence of degeneration of the nigrostriatal dopamine system. Six weeks after 3-AP treatment decreases in both striatal dopamine content and the activity of the catecholamine biosynthetic enzyme tyrosine hydroxylase were observed. Immunohistochemical examination suggested a decreased density of striatal tyrosine hydroxylase-immunoreactive fibers and revealed the emergence of a distinctly patchy organization of the dopamine innervation to the dorsolateral striatum. While 3-AP administration resulted in biochemical and anatomical data consistent with the degeneration of nigrostriatal dopamine fibers, no significant changes in dopamine content or the density or pattern of tyrosine hydroxylase-immunoreactive fibers in the anteromedial prefrontal cortex or nucleus accumbens were seen. These data suggest that 3-AP administration may result in a relatively specific degeneration of the nigrostriatal dopamine system. Since 3-AP causes both a profound loss of the climbing fiber input to the cerebellum derived from the inferior olivary nucleus, and the degeneration of nigrostriatal dopamine neurons, 3-AP administration may provide a useful model of olivopontocerebellar atrophy-associated parkinsonism. Moreover, the differences in the neurotoxicity caused by 3-AP and that elicited by another pyridine which causes striatal dopamine depletion (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP) may offer important insights into the mechanisms of both species- and site-specific pyridine neurotoxins.

Goldthioglucose causes brain norepinephrine and serotonin depletion correlated with increased body weight

Goldthioglucose (GTG) injected i.p. in mice is known to cause hyperphagia and obesity which is related to ventromedial hypothalamic damage and norepinephrine (NE) depletion in females. In the present experiment 6 doses of GTG were tested in males. After 160 days the monoamine content of whole brain was measured. Norepinephrine (NE) and serotonin (SER) were depleted without changes in dopamine content. Brain NE and SER were both negatively correlated with body weight. These experiments extend earlier studies by suggesting that GTG obesity in mice may be caused by NE depletion in males as well as females and by suggesting that the obesity is also a function of serotonin depletion.

Influence of freezer storage time on cerebral biogenic amine and metabolite concentrations and receptor ligand binding characteristics

Brains from breed and age-matched canines stored at -80 °C for between 3 and 44 months showed a time-dependent decline in the concentration of norepinephrine in the amygdala and dopamine and norepinephrine in the caudate. No changes were seen in the density or ligand affinities of prazosin or spiperone binding sites in the same areas nor were there changes in quinuclidinyl benzylate binding sites in the frontal cortex. The changes in dopamine concentrations in the caudate were not accompanied by changes in the concentrations of dopamine metabolites. The chromatograms from which the dopamine and norepinephrine concentrations were estimated contained several unidentified, amperometrically detectable, extraneous peaks which increased in size in the older tissue samples. These results suggest that the decline in dopamine and norepinephrine concentrations was not the result of enzymatic breakdown, but probably the result of chemical decomposition. These findings have significance for the measurement of dopamine and norepinephrine concentrations in autopsied brains kept frozen in storage.

Haemorrhage-induced release of noradrenaline, 5-hydroxytryptamine and uric acid in the supraoptic nucleus of the rat, measured by microdialysis

Concentrations of monoamines and metabolites and uric acid were measured inn sequential 15-min microdialysis samples taken from the area of the supraoptic nucleus (SON) in 9 urethane-anaesthetized rats. A decrease of blood pressure of 40 mm Hg was induced by withdrawing 3–4 ml of blood from an indwelling jugular catheter. This decreased of blood ppressure was maintained for 30 min and produced a significant rise in the concentration of noradrenaline (NA) and its metabolite 4-hydroxy-3-methoxyphenyllethan-1, 2-diol (MPHG) and also in 5-hydroxytryptamine (5-HT) and the purine metabolite uric acid (UA). When blood pressure was returned to normal by replacing the withdrawn blood, the concentration of NA, MHPG, 5-HT and UA returned to pre-haemorrhage levels within 15 min. No significant changes in concentrations of dopamine and its metabolites were found, and in 7 control animals sampled 1.5–2 mm away from the SON, in the area of the olfactory tubercle, concentrations of NA, MHPG, 5-HT and UA were not significantly altered by haemorrhage-induced decreases in blood pressure.

Monoaminergic correlates of kindling

High-performance liquid chromatography with electrochemical detection was used to measure the regional concentrations of monoamines and metabolites in the brains of rats killed 2 or 4 weeks after kindling of generalized seizures with amygdaloid stimulation. each kindled rat was compared to a yoked control that received brief trains of non-convulsive low-frequency stimulation of the amygdala. Two weeks after kindling we found a significant depletion of noradrenaline (NA) in the ipsilateral frontal cortex, a significant depletion of serotonin (5-HT) in the stimulated amygdala and contralateral hypothalamus, and no significant changes in concentration of dopamine (DA). Four weeks after kindling we found significant depletions of NA in the stimulated amygdala and ipsilateral hypothalamus, a significant depletion of 5-HT in the ipsilateral hippocampus, and no significant changes in DA. These findings generally fail to replicate previous reports of monoaminergic correlates of kindling. Furthermore, the alterations in monoamines produced by kindling do not fall into a simple and readily interpretable pattern.

Striatal dopamine activity and unilateral barpressing in rats

A micro-punch tissue assay was used to measure changes in dopamine content at twenty-six sites within the striatum of rats trained to barpress exclusively with one forepaw for food pellets. Analysis of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), was carried out using HPLC with electrochemical detection. The barpress group had a significantly higher DOPAC/DA ratio in both the contralateral and ipsilateral hemispheres when compared to feeding and homecage controls. The DOPAC/DA ratio is considered to be a measure of dopaminergic neuronal activity, thus suggesting a bilateral activation of the neostriatal dopaminergic afferents as a result of the motor performance. Topographical analysis within the barpress group revealed an anterior-posterior, medial-lateral gradient of dopaminergic activity with the posterior and lateral sites showing the greatest increases over the controls. The results of this experiment indicate that localized changes in neuronal activity can be monitored with the micro-punch assay-HPLC/EC technique and that voluntary motor behavior produces an activation of the striatal dopamine system.

Effects of 6-hydroxydopamine on dopamine and noradrenaline content in dog blood vessels and heart. Evidence for a noradrenaline-independent dopamine pool.

The noradrenaline and dopamine depletion induced by 6-hydroxydopamine (6-OHDA) and pargyline plus 6-OHDA was investigated in the heart, mesenteric, renal, splenic and femoral arteries and saphenous vein of the dog. Catecholamine concentrations in plasma were also analyzed in these two experimental conditions. 6-OHDA and pargyline plus 6-OHDA induced a parallel decrease of the noradrenaline and dopamine content in the main trunk of the mesenteric artery, femoral artery and heart. In the proximal branches of the mesenteric artery, renal and splenic arteries 6-OHDA selectively reduced noradrenaline (by 50%) without changes in dopamine levels. Previous treatment with pargyline abolished this selectivity and depleted the tissue levels of both noradrenaline and dopamine by 75%. The noradrenaline and dopamine levels in the saphenous vein were not significantly reduced by 6-OHDA (15%) and pargyline plus 6-OHDA (40%). 6-OHDA and pargyline plus 6-OHDA increased both noradrenaline and adrenaline concentrations in plasma, without significant changes in dopamine concentrations. The present findings suggest: an independent dopamine presence in the proximal branches of the mesenteric artery, renal artery and splenic artery; that noradrenaline and dopamine are in one and the same structure in the heart, femoral artery and the main trunk of the mesenteric artery; the saphenous vein is more resistant to chemical sympathectomy than arterial blood vessels; the changes in plasma catecholamine concentrations are probably related to a compensatory mechanism initiated at the adrenal medulla.

Role of cholinergic system in modulating gamma‐aminobutyric acid and dopamine functions in rat brain

AbstractThe effects of cholinergic and anticholinergic agents on dopamine (DA) and gamma‐aminobutyric acid (GABA) levels in specific rat brain regions were studied. A single injection of physostigmine (2 mg/kg, i.p.) produced no significant effect on the levels of DA and GABA in corpus stritum. Treatment with atropine increased striatal GABA content by 38%, suggesting that decreased cholinergic activity alters the release of GABA. Administration of physostigmine partially antagonized the atropine‐induced rise in GABA level of corpus striatum, indicating that the cholinomimetic agent facilitated GABA release in this region. This increase in GABA content is not associated with any change in DA content in the striatum. To further assess the effect of physostigmine on GABA level, animals were pretreated with amino‐oxyacetic acid (AOAA), an inhibitor of the GABA‐degrading enzyme 4‐aminobutyrate 2‐oxoglutarate transaminase (GAGA‐T). Treatment with AOAA (50 mg/kg) elevated GABA levels in corpus striatum, midbrain, and frontal cortex. In contrast, DA levels were decreased by 25% and 30% in the frontal cortex and corpus striatum, respectively. Administration of physostigmine facilitated GABA release in AOAA‐treated animals resulting in a 16% lowering of GABA levels in striatum. Physostigmine did not change striatal DA in rats pretreated with AOAA. These results suggest that cholinergic interneurons in striatum probably facilitate the functioning of GABAergic neurons, which elicit inhibitory effects on the DA system. The clinical importance of such an interneuronal circuit is discussed.

Ovulatory function and retinal catecholamine concentrations in female rats with and without inherited retinal photoreceptor degeneration.

The timing of the critical period and LH surge during the afternoon of proestrus was unchanged in female rats with degenerated retinal photoreceptors (Hunter and Royal College of Surgeons strains), when compared to female rats with intact retinae (Piebald Virol Glaxo and Wistar strains). Both RCS and Wistar strains responded to constant light (LL) exposure by attaining persistent vaginal cornification at the same rate. In addition, both RCS and Wistar strains regained normal estrous cycles when moved from LL to control lighting (LD). Therefore, an intact retinal photoreceptor layer is not essential for normal ovulatory function. In addition, these results show that the effects of LL on gonadotrophin secretion are mediated through the brain and are not the result of retinal degeneration. Measurements of retinal concentrations of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (Dopac), in Wistar and RCS rats showed that concentrations of both compounds were reduced by LL, and then increased back to control values when animals were moved back into LD. Although the magnitude of the changes in retinal concentrations of DA and Dopac was greater in Wistar than in RCS rats (possibly related to the degeneration which occurs in Wistar but not RCS rats), these results suggest that dopaminergic cells, probably within the amacrine cell population of the retina, respond to different light regimes, perhaps by changes in activity.

Changes in dopamine, noradrenaline and adrenaline in specific septal and preoptic nuclei after acute immobilization stress.

Acute immobilization stress results in changes in the concentration of both dopamine and noradrenaline in specific forebrain limbic system areas, whereas the adrenaline levels remain unchanged. Changes in dopamine concentrations are more restricted than those in noradrenaline concentrations. Dopamine levels are increased in the nucleus preopticus medialis, 2 and 4 h after stress, and decreased in the nucleus septalis lateralis, throughout the acute stress period. The noradrenaline levels are also increased in the nucleus preopticus medialis 2 and 4 h after stress. In most septal stress, and in the nucleus interstitialis striae terminalis, the noradrenaline levels are decreased early during acute stress, but return to normal values after 2-4 h of continuous stress. In the nucleus septalis intermediate, on the other hand, the noradrenaline levels are increased, and the change occurs only after 4 h of stress. These results suggest a participation of both noradrenaline levels are increased, and the change occurs only after 4 h of stress. These results suggest a participation of both noradrenaline levels are increased, and the change occurs only after 4 h of stress. These results suggest a participation of both noradrenaline and dopamine neurons in the central response to the stress reaction and the existence of fast adaptive changes in the metabolism of these biogenic amines in specific areas of the limbic system during stress.

Dopamine levels in hypophysial stalk plasma and prolactin levels in peripheral plasma of the lactating rat: effects of a simulated suckling stimulus.

Secretion of prolactin is tonically inhibited by hypothalamic release of dopamine into the hypophysial portal system. However, the role that changes in dopamine secretion play in altering prolactin secretion after physiologic stimuli is still unknown. The present study was designed to investigate changes in dopamine release into stalk blood during sucking-induced release of prolactin. An increase in prolactin secretion was induced in urethane-anesthetized, lactating rats by a 15-min electrical stimulation of an isolated mammary nerve trunk. This procedure induced a rapid increase in prolactin secretion, and a 7-fold increase in prolactin concentrations was observed within 20-30 min after stimulation began. In unstimulated control rats, prolactin levels remained at baseline values during the period of observation. Then, we measured the effect of this stimulus on the concentration of dopamine in hypophysial stalk plasma. Dopamine concentrations in hypophysial stalk plasma, collected at 15-min intervals before, during and after mammary nerve stimulation, decreased significantly by 20% during stimulation, returned to prestimulation values, and then increased significantly by 20% at 45-60 min. In control rats, no changes in dopamine concentrations were observed. These results demonstrate that a simple, inverse relationship between dopamine secretion and prolactin secretion does not exist during suckling. However, the observed decrease in dopamine secretion during mammary nerve stimulation may be an integral part of a complex mechanism, including other hypothalamic hormones, that lead to the release of prolactin.

Biochemical and histochemical studies of the effect of reserpine in Aplysia californica

1. 1. Biochemical and histochemical studies of the effect of reserpine on dopamine levels in nervous-system tissue of Aplysia californica were performed. 2. 2. High-pressure liquid chromatography measurements revealed that reserpine treatment dramatically reduced ganglionic dopamine levels. 3. 3. The impressive biochemical changes in dopamine content due to reserpine were not accompanied by a change in the pattern or intensity of nervous-system tissue histofluorescence.

Behavioural and biochemical effects of dopamine and noradrenaline depletion within the medial prefrontal cortex of the rat

The effects of 6-hydroxydopamine (6-OHDA) lesions of catecholamine terminals within the medial prefrontal cortex on spontaneous motor activity, dopamine (DA)-dependent stereotyped behaviour and subcortical dopamine turnover were investigated in the rat. Two types of lesions were examined, bilateral injection of 6-OHDA into the medial prefrontal cortex of untreated rats (6-OHDA alone), and bilateral injection of 6-OHDA into the medial prefrontal cortex of animals pretreated with the noradrenaline (NA) uptake blocking agent desmethylimipramine (6-OHDA/-DMI). Ten days after surgery the 6-OHDA lesions produced no significant change in spontaneous motor activity and had no overall effects on stereotyped behaviour induced by apomorphine or (+)-amphetamine. This lesion caused gross depletion of NA within the medial prefrontal cortex and curiously, elevated DA concentrations within this site. No changes in DA concentration were recorded within subcortical sites, although concentrations of DA metabolites within striatum and nucleus accumbens were reduced. In contrast, the 6-OHDA/DMI lesion of the medial prefrontal cortex significantly enhanced spontaneous motor activity and amphetamine-induced stereotyped behaviour. Apomorphine-induced stereotypy, on the other hand, was significantly reduced. Biochemically the lesion caused a large depletion of DA with relatively little loss of NA within the medial prefrontal cortex. In addition, from this and another study (ref. 33), increases in DA and its metabolite concentrations were measured in striatum and nucleus accumbens, together with an apparent increase in DA turnover within these subcortical sites. It is thus apparent that in the absence of a substantial portion of the DA innervation of the medial prefrontal cortex, with a largely intact NA innervation, there is an increase in motor activity and amphetamine-induced stereotypy which may be related to functional changes in DA activity within subcortical telencephalic structures. Such a finding might suggest that DA within the frontal cortex has a behaviourally inhibitory role in the rat, although further work is required to substantiate this.

The spontaneous firing patterns of forebrain neurons. V. Time course of changes in caudate unit activity following dopamine-depleting lesions

The effects of unilateral medial forebrain bundle (‘MFB’) lesions on the spontaneous firing patterns of caudate neurons on both sides of the brain in cats were studied 3 days, 7 days and more than 2 weeks postlesion. Our results indicate that: (1) the spontaneous firing of neurons in the caudate nucleus ipsilateral to the lesion slows significantly by 3 days postlesion and returns to control values by 7 days postlesion, (2) the spontaneous activity of contralateral caudate neurons slows progressively with postlesion time and (3) these changes in neural activity are not correlated with changes in dopamine concentrations in the caudate nucleus.

Effects of baclofen on different dopaminergic neuronal systems

Systemic administration of dl or l-baclofen causes a dose-related increase in the concentration of dopamine (DA), but not of norepinephrine, in the forebrains of mice and rats. Microinjections of baclofen or GABA into substantia nigra increase DA in striatum. Since only the effect of GABA is reversed by picrotoxin, it would appear that baclofen does not act through a GABAergic mechanism. Baclofen-induced changes in DA concentrations are believed due to the depression of neuronal impulse flow which results in a decreased release of DA and thus a concomitant decrease in putative autoreceptor activation. Activation of DA autoreceptors appears to inhibit the synthesis and release of DA. Baclofen increases the concentration and the rate of synthesis of DA (accumulation of DOPA after inhibition of decarboxylase with NSD 1015) in the striatum, olfactory tubercle and posterior pituitary, but not in the median eminence. Apomorphine reverses the baclofen-induced increases in the concentration and synthesis of DA in all brain regions except median eminence, presumably by activating DA autoreceptors. Since baclofen depresses the α-methyltyrosine-induced decline of DA in all brain regions it would appear that tuberoinfundibular nerves, which terminate in the median eminence, differ from other DA nerves in that they are not regulated by autoreceptors.

Experimental hypertension and catecholamine distribution in the rat brain

Hypertension was induced in rats (Hebrew University strain) by three different procedures: (1) deoxycorticosterone acetate (DOCA)--salt treatment; (2) unilateral renal artery clip or (3) chronic salt-loading. Noradrenaline (NA) and dopamine (DA) distribution in different brain areas was assayed following induction of hypertension. NA content increased significantly in various areas: the increase of NA in the pons-medulla was common to all procedures inducing hypertension. NA content increased also in the mesencephalon, the hypothalamus and the rest of the forebrain (DOCA--salt hypertension), in the mesencephalon, the hypothalamus and the cortex (in renal clip hypertension). No significant changes in DA content were observed in any region of the brain following induction of hypertension by the three different methods. In two substrains, selected from the Hebrew University strain, for their respective sensitivity (H) or immunity (N) to hypertension induced by DOCA--salt treatment, there were no significant increases in NA or DA in any part of the brain following DOCA--salt treatment. Comparison of NA concentrations in these strains showed that NA was significantly higher in the pons-medulla of the untreated N strain rats than in the medulla of untreated H strain or in untreated rats of the original strain (Hebrew University). A model is presented suggesting that central NA-containing neurons plays a major role in controlling hypertension.

Assessment of the effects of neonatal subcutaneous 6-hydroxydopamine on noradrenergic and dopaminergic innervation of the cerebral cortex

Female rats, treated at birth with 6-hydroxydopamine (3 × 100mg/kg s.c. at 24 h intervals) or vehicle, were subjected at 112 days of age to unilateral electrolytic lesions of the locus coeruleus. Two weeks later regions of the telencephalon, both ipsiand contralateral to the lesion, were simultaneously assayed for norepinephrine (NE) and dopamine (DA) content, and for tyrosine hydroxylase (TOH) and dopamine-β-hydroxylase (DBH) activities. In the vehicle-treated rats the lesion resulted in at least an 80% reduction of NE and DBH on the ipsilateral side, relative to the contralateral side. TOH was reduced to a similar extent only in the parietal cortex and hippocampus. In the prefrontal cortex and cingulate gyrus TOH was decreased by only 31% and 64% respectively; the remainder was interpreted to be associated with projections of the mesocortical dopamine system. From this data it was possible to calculate that the ratio of TOH to DA in dopaminergic terminals is about 10-fold greater than the ratio of TOH to NE in noradrenergic terminals. Neonatal 6-hydroxydopamine treatment resulted in practically total elimination of noradrenergic terminals throughout the telencephalon, and the locus coeruleus lesion had no additional effect. The drug treatment produced no significant change in DA content or in the TOH to DA ratio in the prefrontal cortex and cingulate gyrus, indicating complete sparing of the mesocortical DA projections.