Dopamine And 3,4-dihydroxyphenylacetic Acid Research Articles

Catechol Concentrations in the Hemolymph of the Scallop, Placopecten magellanicus

Catecholamines have previously been detected in numerous tissues and are thought to control a wide variety of physiological functions in bivalve molluscs. In the present study, alumina extraction and high-performance liquid chromatography reveal the presence of significant concentrations of 3,4-dihydroxyphenylalanine (DOPA), dopamine, and 3,4-dihydroxyphenylacetic acid (DOPAC) in the hemolymph of the sea scallop, Placopecten magellanicus. The concentration of dopamine in the hemolymph averaged 223.8 ng/ml, (±48.4, SEM), equivalent to 10−7 to 10−6 M. Neither epinephrine nor norepinephrine was reliably detected in significant quantities. Previous studies have demonstrated physiological responses to dopamine with thresholds of 10−9 to 10−6 M, thus suggesting that this catecholamine may have an endocrine function. Furthermore, monitoring hemolymph concentrations of catechols might provide a sensitive measure of the physiological status of bivalves. For example, drugs known to affect catechol concentrations in other tissues also effect hemolymph levels. Administration of monoamine oxidase inhibitors such as pargyline, deprenyl, and clorgyline at 10−4 M for 1 day of incubation followed by a 2-day wash resulted in decreased hemolymph concentrations of DOPAC and increased concentrations of its precursors, DOPA and dopamine. Incubation in 10−4 M 3,5-dinitrocatechol, a catecholamine-O-methyl transferase blocker, for 1 day followed by a 2-day wash significantly increased the concentration of dopamine and DOPAC in the hemolymph. Scallops incubated in 10−5 M α-methyl-p-tyrosine, a blocker of tyrosine hydroxylase, for 1 day followed by a 3-day wash in artificial seawater had significantly reduced concentrations of DOPA, dopamine, and DOPAC in the hemolymph. In addition to responding to pharmacological agents, dopamine levels also decreased significantly following thermal induction of spawning, thus suggesting that hemolymph concentrations of catechols might provide indices of reproductive activity and/or stress.

Effect of Melatonin Treatment on 24-hour Variations in Hypothalamic Serotonin and Dopamine Turnover During the Preclinical Phase of Freund's Adjuvant Arthritis in Rats

The effect of melatonin treatment on time-of-day variations in hypothalamic serotonin (5-HT) and dopamine (DA) turnover was studied in rats treated with Freund's complete adjuvant (FCA). Animals received s.c. injections of 30 æg of melatonin or vehicle 1 h before lights off for 11 days. On day 10 of treatment, FCA or its vehicle was s.c. injected, and 2 days later, the rats were killed at 6 different time intervals throughout a 24-hour cycle. Hypothalamic 5-HT, 5-hydroxyindole-3-acetic acid (5-HIAA), DA and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured by HPLC. 5-HT and DA turnover were estimated from the 5-HIAA/5-HT and DOPAC/DA ratios, respectively. In the anterior hypothalamus, time-of-day variation in 5-HT turnover was suppressed by FCA, an effect counteracted by melatonin treatment. Melatonin also prevented FCA effect on medial hypothalamic 5-HT turnover, while in the posterior hypothalamus, similar daily variations of 5-HT turnover were found in all experimental groups. As far as DA turnover, FCA or melatonin administration suppressed its daily variations in the anterior hypothalamus. Time-of-day variations in medial hypothalamic DA turnover were similar in all groups while only rats treated with melatonin and FCA or its vehicle exhibited significant daily changes of DA turnover in the posterior hypothalamus. Results indicate that melatonin treatment affects partly the 24-hour pattern of variation of hypothalamic 5-HT and DA turnover at an early phase of FCA arthritis in rats.

Role of striatal serotonin2A and serotonin2C receptor subtypes in the control of in vivo dopamine outflow in the rat striatum.

This study investigated, using in vivo microdialysis in the striatum of freely moving rats, the role of striatal serotonin2A (5-HT2A) and 5-HT2C receptor subtypes in the modulation of dopamine (DA) and 3, 4-dihydroxyphenylacetic acid (DOPAC) outflow, both in basal conditions and under activation induced by subcutaneous administration of 0.01 mg/kg haloperidol. The different 5-HT2 agents used were applied intrastriatally at a 1 microM concentration through the microdialysis probe. Basal DA efflux was enhanced (27%) by the 5-HT2A/2B/2C agonist 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI) and reduced (-30%) by the 5-HT2B/2C antagonist SB 206553. It was unaffected by infusion of the 5-HT2A antagonist SR 46349B. The effect of DOI was abolished by SB 206553 but not modified by SR 46349B. Haloperidol-stimulated DA efflux (65-70%) was reduced by both SR 46349B (-32%) and the 5-HT2A/2B/2C antagonist ritanserin (-30%) but not affected by SB 206553. Conversely, the effect of haloperidol was potentiated (22%) when DOI was coperfused with SB 206553. Also, haloperidol-stimulated DOPAC outflow (40-45%) was reduced (-20%) by SR 46349B and potentiated (25%) by the combination of SB 206553 with DOI. These results indicate that striatal 5-HT2A receptors, probably through activation of DA synthesis, positively modulate DA outflow only under activated conditions. In contrast, striatal 5-HT2C receptors exert a facilitatory control on basal DA efflux, which appears to be both tonic and phasic.

Immunoneutralization of prolactin prevents stimulatory feedback of prolactin on hypothalamic neuroendocrine dopaminergic neurons.

We have found that exogenous prolactin (PRL) stimulates all three populations of hypothalamic neuroendocrine dopaminergic neurons. In this study, we investigated the effects of immunoneutralization of endogenous PRL on the activity of these neurons. Injection of 17beta-estradiol (E2) (20 microg subcutaneously) 10 d after ovariectomy induced a proestrus-like increase in PRL in peripheral plasma the following afternoon. At 1000 h the day after E2 injection, rats received either rabbit antirat PRL antiserum (PRL-AS) (200 microL) or normal rabbit serum (NRS, 200 microL, controls) intraperitoneally. Groups of rats were then decapitated every 2 h from 1100 h to 2100 h. Trunk blood was collected and serum extracted with protein A to remove the PRL-AS/PRL complex, and the remaining free PRL was measured by radioimmunoassay. Sites of neuroendocrine dopaminergic nerve terminals, the median eminence (ME), and intermediate and neural lobes of the pituitary gland were excised and stored for determination of dopamine (DA) and 3,4-dihydroxyphenyl acetic acid (DOPAC) concentrations by high-performance liquid chromatography electrochemical detection (EC). In addition, the anterior lobe of the pituitary gland, the locus of DA action, was collected. The concentration of PRL in NRS-treated animals increased by 1500 h, peaked by 1700 h, and returned to low levels by 2100 h. PRL-AS prevented the increase in PRL secretion in response to E2. The turnover of DA (DOPAC:DA ratio; an index of dopaminergic neuronal activity) in the ME of NRS-treated animals increased at 1500 h and rapidly returned to basal levels. Treatment with PRL-AS prevented the increase in DA turnover in the ME. DA turnover in the intermediate lobe increased coincident with the peak of PRL in serum of NRS-treated rats. PRL-AS administration prevented increased DA turnover in the intermediate lobe. The turnover of DA in the neural lobe increased by 1300 h and decreased steadily through 2100 h. However, administration of PRL-AS minimally suppressed the turnover of DA in the neural lobe. Moreover, administration of PRL-AS attenuated the rise of DA in the anterior lobe associated with the waning phase of the E2-induced PRL surge. These results clearly indicate that endogenous PRL regulates its own secretion by activating hypothalamic neuroendocrine dopaminergic neurons.

Effects of melatonin on dopamine metabolism in the hypothalamus and the pituitary of the rainbow trout,Oncorhynchus mykiss

The present paper discusses the effect of a single melatonin treatment (0.5 mg/kg, i.p.) on the dopaminergic metabolism in the hypothalamus and pituitary of the rainbow trout. The effects of exogenous melatonin on dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents were compared with the variations in the content of these catecholamines associated to the natural increase in the endogenous melatonin from daytime (3 hr before lights off) to nighttime (3 hr after lights off). Animals treated with melatonin showed a rapid (maximal values at 30 min post-injection) and relatively sustained rise in plasma melatonin levels, which reached supraphysiological ranges. The increase in circulating melatonin was accompanied by a reduction in the amount of DOPAC in both the hypothalamus (30, 60, and 120 min after i.p. melatonin) and the pituitary (120 min after i.p. melatonin) as well as in the pituitary DOPAC/DA ratio (60 and 120 min after i.p. melatonin). Similarly, the increase in circulating melatonin levels from the daytime to nighttime was associated with decreases in the contents of DOPAC in both the hypothalamus and pituitary and in the DOPAC/DA ratio in the pituitary. These data suggest that the inhibition of the hypothalamic-pituitary dopaminergic metabolism may be a specific mechanism of melatonin action in the trout brain that might operate following changes in the secretion of the hormone from the pineal gland.

Melatonin fails to protect against long-term MPTP-induced dopamine depletion in mouse striatum.

Several laboratories recently have reported that melatonin may possess neuroprotective properties. The present paper presents the results of our studies on the long term in vivo neuroprotective effects of melatonin in a well-defined neurotoxicity model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the C57BL/6 mouse. MPTP is bioactivated by brain monoamine oxidase B (MAO-B) to its neurotoxic pyridinium metabolite 1-methyl-4-phenylpyridinium (MPP(+)) which destroys dopaminergic nerve terminals leading to the depletion of neostriatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC). Our initial study compared striatal DA and DOPAC levels in MPTP-only-treated animals and animals treated with melatonin 30 min prior to and 3 times hourly post-MPTP. DA/DOPAC levels measured 7 days after MPTP were similar in both groups. A second study was designed to address the possibility that melatonin cleared from the brain prior to MPP(+). Animals, that had been administered the same regimen of melatonin as in the first study plus a fourth post-MPTP melatonin dose, were maintained on melatonin in drinking water until 5 days post-MPTP. Striatal DA/DOPAC levels of these melatonin-plus-MPTP treated animals also were the same as the MPTP-only-treated animals. In vitro studies confirmed that melatonin is not an inhibitor of MAO-B. These data demonstrate that melatonin does not have any significant protective effects against the long-term striatal DA and DOPAC depletion induced by MPTP in the C57BL/6 mouse.

Lesion of the substantia nigra pars compacta downregulates striatal glutamate receptor subunit mRNA expression

This is a study of the effect of the unilateral administration of dopamine (DA) in the pars compacta of the substantia nigra (SN) of the rat on striatal glutamate receptor subunit (GluR1, GluR2 and NMDAR1) gene expression determined by in situ hybridization. The location of the nigral lesion was determined by tyrosine hydroxylase (TH) immunohistochemistry and its extent by the striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations. The DA-induced lesions produce significant bilateral reductions in the expression of GluR1 and NMDAR1 subunit mRNA in the medio-lateral striatum, whereas the expression of striatal GluR2 receptors was not changed. The reduction in GluR1 and NMDAR1 subunit mRNA may be the consequence of glutamatergic hyperactivity developed in the presence of a damaged nigro-striatal system and these may be associated with the genesis of some neurodegenerative diseases.

Dual effects of l-3,4-dihydroxyphenylalanine on aromatic l-amino acid decarboxylase, dopamine release and motor stimulation in the reserpine-treated rat: evidence that behaviour is dopamine independent

The comparative effects of l-3,4-dihydroxphenylalanine (L-DOPA) on dopamine synthesis, release and behaviour were studied in the reserpine-treated rat. Acute administration of L-DOPA (25–200 mg/kg) dose-dependently inhibited the activity of aromatic l-amino acid decarboxylase (AADC) in the substantia nigra and corpus striatum. The antiparkinsonian drugs budipine (10 mg/kg) and amantadine (40 mg/kg) enhanced AADC activity in these regions, and prevented or reversed AADC inhibition by L-DOPA. Dual probe dialysis revealed that low doses of L-DOPA (25–50 mg/kg) dose-dependently stimulated the release of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in nigra and striatum, whilst high doses of L-DOPA (100–200 mg/kg) completely suppressed the release of dopamine, but not DOPAC. Sulpiride (50 μM) administered via the probes antagonized dopamine release in response to 25 mg/kg L-DOPA, but greatly facilitated release by 200 mg/kg L-DOPA. Dopamine release was blocked by the centrally acting AADC inhibitor NSD 1015, but facilitated by the central AADC activator budipine. In behavioural tests L-DOPA (plus benserazide, 50 mg/kg) only reversed akinesia at 200 mg/kg, and not at 25–100 mg/kg. Pretreatment with either NSD 1015 (100 mg/kg) or budipine (10 mg/kg) markedly potentiated the motor stimulant action of a threshold dose of L-DOPA (100 mg/kg). A combination of NSD 1015 (100 mg/kg) and benserazide (50 mg/kg) potentiated L-DOPA behaviour more effectively than either inhibitor alone. NSD 1015-facilitated L-DOPA behaviour was antagonized by sulpiride (100 mg/kg) and not by SCH 23390 (1 mg/kg), whereas budipine-facilitated L-DOPA behaviour was fully antagonized by SCH 23390 and only partially by sulpiride. These results show that behaviourally active doses of L-DOPA in the reserpinized rat are not accompanied by significant increases in extracellular dopamine and are therefore probably not dopamine mediated. We propose that L-DOPA is capable of directly stimulating dopamine D 2 and possibly non-dopamine receptors, thereby inhibiting dopamine efflux presynaptically and promoting motor activation postsynaptically. A stimulant action of L-DOPA on motor behaviour, preferentially mediated by D 1>D 2 receptors, suggests that L-DOPA may also be capable of yielding a dopamine-like response in the absence of detectable dopamine release. These findings are incorporated into a new model of L-DOPA's actions in the reserpinized rat, and their possible implications for our understanding of L-DOPA in Parkinson's disease are discussed.

A simple high-performance liquid chromatography assay for simultaneous determination of plasma norepinephrine, epinephrine, dopamine and 3,4-dihydroxyphenyl acetic acid

A reversed-phase HPLC assay coupled with electrochemical detection for simultaneously measuring plasma levels of norepinephrine, epinephrine, dopamine, and 3,4-dihydroxyphenylacetic acid (DOPAC) was developed. Separation of the catecholamines and the internal standard isoproterenol was obtained by a mobile phase consisting of 7% methanol in 0.1 M citrate buffer containing 0.3 mM sodium ethylenediaminetetraacetic acid (EDTA), and 0.5 mM 1-octanesulfonic acid, operated under isocratic condition at a flow rate of 1.2 ml/min. The potential of the guard cell was set at +650 mV, the first electrode of the analytical cell at +100 mV and the second at +350 mV. Using a signal-to-noise ratio of >3, the minimum detection limit assessed by direct on column injection was <10 pg for analyte. The assays were linear from basal concentrations to 400 ng/ml. The intra- and inter-assay variations were <10 and 15%, respectively. The assay has been applied successfully to measure plasma concentrations of these catecholamines in humans, rabbits and rats.

Prolactin activates all three populations of hypothalamic neuroendocrine dopaminergic neurons in ovariectomized rats

Prior studies suggest that prolactin (PRL) stimulates release of dopamine (DA) from tuberoinfundibular dopaminergic (TIDA) neurons. In the present study, the time course over which PRL exerts its effects on all three populations of neuroendocrine dopaminergic (DAergic) neuron populations [TIDA, tuberohypophyseal (THDA) and periventricular-hypophyseal (PHDA)] was determined. Ten days following ovariectomy (OVX), groups of female rats were injected either with 15 μg of ovine PRL (oPRL) or saline at 0900 h. Rats were decapitated every 30 min from 0830 h–1100 h and hourly from 1200 h–1500 h. Trunk blood was assayed for rat PRL (rPRL) and oPRL using species-specific radioimmunoassays (RIAs). The concentration of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence (ME), as well as the anterior (AL), intermediate (IL) and neural (NL) lobes of the pituitary gland were determined by HPLC-EC. The concentration of rPRL in oPRL-treated animals, compared to saline-treated animals, was diminished by 1000 h and again between 1200 h–1500 h. DOPAC/DA ratio, an indicator of dopaminergic neuronal activity, increased spontaneously in the ME, IL, and NL during the afternoon in OVX rats. In animals injected with oPRL at 0900 h, the DOPAC/DA ratio increased in the ME, IL and NL within 1 h. Moreover, a secondary increase in the DOPAC/DA ratio in the IL and NL occurred during the afternoon in oPRL-treated rats. However, the second increase of DA turnover present in the ME of control animals never occurred in oPRL-treated animals. Furthermore, there were two increases in the concentration of DA in the AL: the first coincided with the increased turnover of DA in all three terminal areas and the second with increased DA turnover in the IL and NL. These data suggest that all three populations of hypothalamic neuroendocrine DAergic neurons are activated by PRL and that PHDA/THDA neurons have a second `delayed' activation.

Day- and night-time contents of monoamines and their metabolites in the medial preoptic area of the rat hypothalamus

The present study was conducted to investigate whether monoamines and their metabolites in the medial preoptic area (mPOA) of the rat hypothalamus exhibit differences in their contents between day and night. We therefore sampled the mPOA from adult animals of either sex at the middle of the light or dark period, respectively, and analyzed the tissue by means of high performance liquid chromatography with electrochemical detection. We found that, in female animals at mid-night, dopamine and 3,4-dihydroxyphenyl acetic acid (DOPAC) was reduced to 43 and 30%, respectively, of daytime levels, while the norepinephrine content was doubled. No significant differences were observed in male animals. We also conducted immunohistochemistry of the catecholamine synthesizing enzymes, tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), in sections from perfusion-fixed male rats and showed that TH is present in neuronal perikarya and processes in the anteroventral periventricular region of the mPOA, while DBH was only seen in fibers and terminals. Our results of sex-specific and day time-dependent variations in dopamine and norepinephrine concentrations indicate that the two monoamines are candidate neurotransmitters that may transmit diurnal information to the mPOA.

Conjugates of catecholamines with cysteine and GSH in Parkinson's disease: possible mechanisms of formation involving reactive oxygen species.

Oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) and dopamine (DA) to generate semiquinones/quinones, oxygen radicals, and other reactive oxygen species may play a role in neuronal cell death in Parkinson's disease (PD). In particular, semiquinones/quinones can form conjugates with thiol compounds such as GSH and cysteine. Exposure of L-DOPA, DA, and other catecholamines to a system generating O2.- radical led to O2(.-)-dependent depletion of added GSH (or cysteine), accompanied by the formation of thiol-DA or -DOPA adducts as detected by HPLC. Superoxide could additionally cause destruction of these adducts. Iron or copper ions could also promote conjugate formation between GSH or cysteine and DA and L-DOPA, especially if H2O2 was present. We applied HPLC to measure glutathionyl and cysteinyl conjugates of L-DOPA, DA, and 3,4-dihydroxyphenylacetic acid (DOPAC) in postmortem brain samples from PD patients and normal control subjects. Conjugates were detected in most brain areas examined, but levels were highest in the substantia nigra and putamen. In most regions, adduct levels were lower in PD, but there were significant increases in cysteinyl adducts of L-DOPA, DA, and DOPAC in PD substantia nigra, suggesting that acceleration of L-DOPA/DA oxidation occurs in PD, although we cannot say if this is a primary feature of the disease or if it is related to therapy with L-DOPA. In vitro, conjugate formation could be inhibited by the dithiol dihydrolipoate but not by its oxidised form, lipoic acid.

Dopamine Autoreceptors in Rat Nucleus Accumbens Modulate Prepulse Inhibition of Acoustic Startle

Dopamine and 3,4-dihydroxy phenylacetic acid (DOPAC) levels in discrete regions and apomorphine- or (−)-sulpiride–induced changes in electrically evoked dopamine release from nucleus accumbens slices were assessed after testing prepulse inhibition of acoustic startle (PPI) in rats. Dopamine and DOPAC levels in the nucleus accumbens, but not in the striatum, correlated well with PPI ( r = −0.64 for dopamine, r = −0.48 for DOPAC). Evoked dopamine release from the nucleus accumbens did not differ between the high-PPI (more than 60%) and the low-PPI (less than 40%) group. When slices were superfused with 1 μM apomorphine, the S2/S1 ratio in rats showing high PPI was 0.77 ± 0.02 (mean ± SEM, 66% of control), significantly smaller than in the low-PPI group (S2/S1 ratio = 0.97 ± 0.08, 94% of control, p < 0.05). Moreover, (−)-sulpiride–induced increase in evoked dopamine release from the nucleus accumbens in the high-PPI group was inclined to be greater than in the low-PPI group. The results suggest that PPI differences between individuals may reflect the sensitivity of release-modulating dopamine autoreceptors in the nucleus accumbens.

Unique activation of extracellular striato-pallidal neurotransmitters in rats following acute risperidone

The present study investigated the effects of the putative atypical antipsychotic drug (APD), risperidone, on striatal monoamine and pallidal γ-aminobutyric acid (GABA) function using dual probe in vivo microdialysis. Risperidone (0.03, 0.3, 3 mg/kg) or vehicle was injected (s.c.) into female, Sprague–Dawley rats fitted with dual microdialysis probes in the striatum and the globus pallidus (GP). In the striatum, risperidone increased extracellular levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) at all doses and the serotonin (5-HT) metabolite, 5-hydroxyindoleacetic acid (5-HIAA), at the highest dose. The increase in striatal DA was most pronounced at the lowest dose of risperidone; however, DOPAC showed a dose dependent increase. Risperidone at the medium and high doses significantly reduced extracellular GABA levels in the GP. Simultaneous measurement of limb rigidity during microdialysis showed that risperidone dose-dependently produced significant increases in horizontal bar test catalepsy and fore- and hindlimb paw retraction latencies. The current results suggest novel effects of risperidone on striatal DA release, while the pallidal GABA changes are similar to previous results obtained with the atypical antipsychotic drug, clozapine. Additionally, the behavioral results predict the clinical expression of extrapyramidal motor side effects at high doses. Overall, these results support an atypical profile of risperidone when compared with typical APDs, yet one with unique neurochemical and behavioral properties.

Methamphetamine-induced modification of dopamine metabolism in cultured striatal astrocytes.

The role of striatal astrocytes in the metabolic processing (by deamination) of methamphetamine-released dopamine is not known. To investigate the relationship between methamphetamine and dopamine metabolism, we measured 6-hydroxydopamine, dopamine and, 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations following methamphetamine treatment of cultured striatal astrocytes prepared from 1-2 day-old rats. Addition of low concentrations of dopamine (5 x 10(-5) to 5 x 10(-4) M) to cultured astrocytes increased DOPAC levels in a dose-dependent fashion while higher concentrations (5 x 10(-3) to 10(-2) M) inhibited its metabolism and induced formation of 6-hydroxydopamine. Under the same experimental conditions, 10(-4) M dopamine in combination with methamphetamine (10(-5) to 10(-3) M) inhibited DOPAC formation and increased dopamine levels in a dose-dependent fashion, but the formation of intracellular 6-hydroxydopamine was not evident. Deprenyl (10(-5) or 10(-4) M), an inhibitor of monoamine oxidase B, and pargyline (10(-5) or 10(-4) M), a non-selective monoamine oxidase inhibitor, completely inhibited DOPAC formation and increased dopamine levels, while clorgyline (10(-5) or 10(-4) M), an inhibitor of monoamine oxidase-A, only partially inhibited DOPAC formation (42 or 45% of control, respectively). These results support the hypothesis that methamphetamine inhibits monoamine oxidase and causes increases in dopamine levels in cultured striatal astrocytes.

L-DOPA does not facilitate nitric oxide production in the rat striatum and substantia nigra: In vivo microdialysis study

Using in vivo microdialysis and flow-injection, we evaluated the production of nitric oxide (NO) in the striatum and substantia nigra of freely moving rats in response to challenge doses of l-dihydroxyphenylalanine ( l-DOPA) by measuring the NO metabolite levels of nitrate and nitrite. The dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations also were determined in the same perfusates. Intraperitoneal injection of l-DOPA produced a significant, dose-dependent increase in the extracellular levels of dopamine and DOPAC in these areas, but did not modify the extracellular levels of the NO metabolites. An acute dose of l-DOPA does not appear to facilitate NO production in the rat striatum and substantia nigra.

Serotonin is reduced in the frontal cortex of Sardinian ethanol-preferring rats.

Ethanol-naive Sardinian alcohol-preferring (sP) and Sardinian alcohol-non-preferring (sNP) rats were tested to evaluate the levels of serotonin (5-HT) and 5-hydroxyindol-3-yl-acetic acid (5-HIAA) in the frontal cortex, hypothalamus, and nucleus accumbens, and the levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the hypothalamus and nucleus accumbens. Compared with the sNP line, the sP rats had lower 5-HT and 5-HIAA concentrations in the frontal cortex, whereas no differences were found in the other brain areas tested, neither for neurotransmitters nor their metabolites. As the decreased 5-HT function is a feature shared by different alcohol-preferring strains, it could be linked to the genetic predisposition to voluntary ethanol consumption.

Effects of prenatal methylazoxymethanol treatment on striatal dopaminergic systems in rat brain

To further examine the effects of prenatal methylazoxymethanol (MAM) treatment on striatal dopaminergic systems, the status of presynaptic dopamine transporters was examined by quantitative autoradiography of [ 3H]GBR 12935 binding. Significantly higher [ 3H]GBR 12935 binding was seen in MAM-lesioned striatum in comparison to the controls, indicating relative dopaminergic hyperinnervation in MAM-induced hypoplastic striatum. The effect of prenatal MAM treatment on extracellular levels of dopamine and its metabolites in the striatum was also examined using in vivo microdialysis. As measured in conscious freely-moving rats, prenatal MAM treatment significantly increased basal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) release in the striatum in comparison with control rats. These data suggest that in accordance with morphological dopaminergic hyperinnervation, dopaminergic functions are significantly augmented in MAM-lesioned brains. Thus, it is suggested that MAM-induced microencephalic rats should serve as a good animal model for the study of augmented dopaminergic functions in the striatum.

The effects of nicotine on dopamine and DOPAC output from rat striatal tissue

The effects of varying doses of nicotine infusion upon spontaneous (basal) and subsequent potassium chloride-stimulated dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) output from superfused corpus striatal tissue fragments of male rats were tested. Spontaneous dopamine and DOPAC outputs were increased in response to 1, 5 and 10, but not to 0.1 and 0 (control) μM concentrations of nicotine. Interestingly, the subsequent K +-stimulated (30 mM) dopamine output was completely abolished in preparations infused with the 5 and 10 μM nicotine, but not with the 1 or 0.1 μM nicotine. No overall significant differences in K +-stimulated DOPAC were obtained among the five doses. In experiment 2, the effects of an initial infusion of amphetamine (10 μM), potassium chloride (30 mM), nicotine (10 μM) or normal superfusion medium (control) were compared upon subsequent K +-evoked dopamine release. The amount of dopamine released in response to the second (subsequent) infusion of K + was significantly greater in the potassium chloride and control conditions versus the nicotine and amphetamine stimulated groups. No overall differences in DOPAC output were observed among the four conditions of experiment 2. These results demonstrate that nicotine can exert differential modulatory effects upon striatal dopaminergic activity as a function of the dose. The augmented levels of DOPAC output along with the abolition of the K +-stimulated dopamine release in response to the 5 and 10 μM nicotine doses suggest that these doses may simultaneously produce an activation of intraneuronal metabolism of dopamine to DOPAC along with an activation of release and inhibition of uptake to diminish stores available for subsequent responses to K + stimulation.

Increase in monoamine levels caused by emotional stress in mice brain regions is attenuated by Saiko-ka-ryukotsu-borei-to.

The effect of Saiko-ka-ryukotsu-borei-to (SRBT) on the stress-induced increase of monoamines in brain regions was investigated in three mouse emotional stress models. Dopamine (DA) and 3,4-dihydroxy-phenyl acetic acid (DOPAC) contents were elevated significantly by electric shock stress, psychological stress and conditioned fear stress in thalamus, hypothalamus and amygdala. The DA and DOPAC levels were decreased by preadministration of SRBT (600 mg/kg, p.o.) in the last two models, but were not altered in electric shock stress. Therefore, this compound seems to be effective in stress involving emotional factors. These results indicate that SRBT affects the brain monoamine neurons leading to psychological change in mice.