DA) And 3,4-dihydroxyphenylacetic Acid Levels Research Articles

Improvement effect of cinnamaldehyde on reserpine-induced Parkinson's disease rat model

In order to study the neuroprotective mechanism of cinnamaldehyde on reserpine-induced Parkinson's disease(PD) rat models, 72 male Wistar rats were randomly divided into blank group, model group, Madopar group, and cinnamaldehyde high-, medium-, and low-dose groups. Except for the blank group, the other groups were intraperitoneally injected with reserpine of 0.1 mg·kg~(-1) once every other morning, and cinnamaldehyde and Madopar solutions were gavaged every afternoon. Open field test, rotarod test, and oral chewing movement evaluation were carried out in the experiment. The brain was taken and fixed. The positive expression of dopamine receptor D1(DRD1) was detected by TSA, and the changes in neurotransmitters such as dopamine(DA) and 3,4-dihydroxyphenylacetic acid(DOPAC) in the brain were detected by enzyme-linked immunosorbent assay(ELISA). The protein and mRNA expression levels of tyrosine hydroxylase(TH) and α-synuclein(α-Syn) in substantia nigra(SN) were detected by RT-PCR and Western blot. The results showed that after the injection of reserpine, the hair color of the model group became yellow and dirty; the arrest behavior was weakened, and the body weight was reduced. The spontaneous movement and exploration behavior were reduced, and the coordination exercise ability was decreased. The number of oral chewing was increased, but the cognitive ability was decreased, and the proportion of DRD1 positive expression area in SN was decreased. The expression of TH protein and mRNA was down-regulated, and that of α-Syn protein and mRNA was up-regulated. After cinnamaldehyde intervention, it had an obvious curative effect on PD model animals. The spontaneous movement behavior, the time of staying in the rod, the time of movement, the distance of movement, and the number of standing times increased, and the number of oral chewing decreased. The proportion of DRD1 positive expression area in SN increased, and the protein and mRNA expression levels of α-Syn were down-regulated. The protein and mRNA expression levels of TH were up-regulated. In addition, the levels of DA, DOPAC, and homovanillic acid(HVA) neurotransmitters in the brain were up-regulated. This study can provide a new experimental basis for clinical treatment and prevention of PD.

Myopia control in Mendelian forms of myopia.

To study the effectiveness of high-dose atropine for reducing eye growth in Mendelian myopia in children and mice. We studied the effect of high-dose atropine in children with progressive myopia with and without a monogenetic cause. Children were matched for age and axial length (AL) in their first year of treatment. We considered annual AL progression rate as the outcome and compared rates with percentile charts of an untreated general population. We treated C57BL/6J mice featuring the myopic phenotype of Donnai-Barrow syndrome by selective inactivation of Lrp2 knock out (KO) and control mice (CTRL) daily with 1% atropine in the left eye and saline in the right eye, from postnatal days 30-56. Ocular biometry was measured using spectral-domain optical coherence tomography. Retinal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured using high-performance liquid chromatography. Children with a Mendelian form of myopia had average baseline spherical equivalent (SE) -7.6± 2.5D and AL 25.8± 0.3 mm; children with non-Mendelian myopia had average SE -7.3± 2.9 D and AL 25.6± 0.9 mm. During atropine treatment, the annual AL progression rate was 0.37 ± 0.08 and 0.39 ± 0.05 mm in the Mendelian myopes and non-Mendelian myopes, respectively. Compared with progression rates of untreated general population (0.47 mm/year), atropine reduced AL progression with 27% in Mendelian myopes and 23% in non-Mendelian myopes. Atropine significantly reduced AL growth in both KO and CTRL mice (male, KO: -40 ± 15; CTRL: -42 ± 10; female, KO: -53 ± 15; CTRL: -62 ± 3μm). The DA and DOPAC levels 2 and 24 h after atropine treatment were slightly, albeit non-significantly, elevated. High-dose atropine had the same effect on AL in high myopic children with and without a known monogenetic cause. In mice featuring a severe form of Mendelian myopia, atropine reduced AL progression. This suggests that atropine can reduce myopia progression even in the presence of a strong monogenic driver.

Recovery of dopaminergic amacrine cells after strobe light stimulation in the developing rat retina

Concerns regarding the impact of strobe light on human health and life have recently been raised. Sources of strobe light include visual display terminals, light-emitting diodes, and computer monitors. Strobe light exposure leads to visual discomfort, headaches, and poor visual performance and affects the number of dopaminergic amacrine cells (DACs) in the developing retina, as well as retinal dopamine levels in animals. DACs serve as the sole source of retinal dopamine, and dopamine release from the retina is activated by light exposure following a circadian rhythm. Using a Sprague-Dawley rat model, this study sought to determine whether changes in DACs caused by strobe light are recoverable after ceasing strobe light exposure during retinal development. From eye opening (postnatal 2 weeks), rats in the control group were reared under normal light (an unflickering 150 lux incandescent lamp with a 12 h light/dark cycle), whereas those in the experimental group (i.e., strobe-recovery group) were reared under strobe light (2 Hz for 12 h/day) exposure for 2 weeks. After postnatal week 4, normal light was provided to all animals to observe the reversibility of the effect of strobe light. Immunohistochemistry and immunoblot analysis for the rate limiting enzyme for dopamine synthesis, tyrosine hydroxylase (TH), as well as high-pressure liquid chromatography for measuring dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were performed at postnatal weeks 4, 6, 8, and 10. The number of type I and type II TH-immunoreactive (TH-IR) cells across the entire retina was counted to evaluate whether changes in DACs induced by strobe light could recover after ceasing strobe light exposure. The number of type I TH-IR cells slightly decreased but remained at a constant level in the control group. In contrast, the number of type I TH-IR cells rapidly decreased up to postnatal week 6, but then increased after postnatal week 8 in the strobe-recovery group. Subsequently, the number of type I TH-IR cells eventually reached a number similar to that in the control group. In addition, the number of intermediate-sized TH-IR cells were increased at postnatal weeks 8 and 10 and the dopamine level was decreased at postnatal week 8 in the strobe-recovery group. However, the levels of DOPAC and TH proteins did not differ between the two groups. This suggests that changes in DACs caused by strobe light are reversible and that type II TH-IR cells may play a key role in this recovery.

Studies on the interactions of retinal dopamine with choroidal thickness in the chicken

PurposeRecently, an increasing number of studies relied on the assumption that visually induced changes in choroidal thickness can serve as a proxy to predict future axial eye growth. The retinal signals controlling choroidal thickness are, however, not well defined. We have studied the potential roles of dopamine, released from the retina, in the choroidal response in the chicken.MethodsChanges in retinal dopamine release and choroidal thickness changes were induced by intravitreal injections of either atropine (250 µg or 360 nMol), atropine combined with a dopamine antagonist, spiperone (500 µMol), or spiperone alone and were tracked by optical coherence tomography (OCT). To visually stimulate dopamine release, other chicks were exposed to flicker light of 1, 10, or 400 Hz (duty cycle 0.2) and choroidal thickness was tracked. In all experiments, dopamine and 3,4-Dihydroxyphenylacetic acid (DOPAC) were measured in vitreous, retina, and choroid by high-performance liquid chromatography with electrochemical detection (HLPC-ED). The distribution of the rate-limiting enzyme of dopamine synthesis, tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS), vascular endothelial growth factor (VEGF), and alpha2A adrenoreceptors (alpha2A-ADR) was studied in the choroid by immunofluorescence.ResultsThe choroid thickened strongly in atropine-injected eyes, less so in atropine + spiperone–injected eyes and became thinner over the day in spiperone alone-, vehicle-, or non-injected eyes. Flickering light at 20 lx, both 1 and 10 Hz, prevented diurnal choroidal thinning, compared to 400 Hz, and stimulated retinal dopamine release. Correlation analysis showed that the higher retinal dopamine levels or release, the thicker became the choroid. TH-, nNOS-, VEGF-, and alpha2A adrenoreceptor–positive nerve fibers were localized in the choroid around lacunae and in the walls of blood vessels with colocalization of TH and nNOS, and TH and VEGF.ConclusionsRetinal DOPAC and dopamine levels were positively correlated with choroidal thickness. TH-positive nerve fibers in the choroid were closely associated with peptides known to play a role in myopia development. Findings are in line with the hypothesis that dopamine is related to retinal signals controlling choroidal thickness.

β-Methylphenylalanine exerts neuroprotective effects in a Parkinson's disease model by protecting against tyrosine hydroxylase depletion.

We evaluated the neuroprotective effects of β‐methylphenylalanine in an experimental model of rotenone‐induced Parkinson's disease (PD) in SH‐SY5Y cells and rats. Cells were pre‐treated with rotenone (2.5 µg/mL) for 24 hours followed by β‐methylphenylalanine (1, 10 and 100 mg/L) for 72 hours. Cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), mitochondrial fragmentation, apoptosis, and mRNA and protein levels of tyrosine hydroxylase were determined. In a rat model of PD, dopamine (DA) and 3,4‐dihydroxyphenylacetic acid (DOPAC) levels, bradykinesia and tyrosine hydroxylase expression were determined. In rotenone–pre‐treated cells, β‐methylphenylalanine significantly increased cell viability and MMP, whereas ROS levels, apoptosis and fragmented mitochondria were reduced. β‐Methylphenylalanine significantly increased the mRNA and protein levels of tyrosine hydroxylase in SH‐SY5Y cells. In the rotenone‐induced rat model of PD, oral administration of β‐methylphenylalanine recovered DA and DOPAC levels and bradykinesia. β‐Methylphenylalanine significantly increased the protein expression of tyrosine hydroxylase in the striatum and substantia nigra of rats. In addition, in silico molecular docking confirmed binding between tyrosine hydroxylase and β‐methylphenylalanine. Our experimental results show neuroprotective effects of β‐methylphenylalanine via the recovery of mitochondrial damage and protection against the depletion of tyrosine hydroxylase. We propose that β‐methylphenylalanine may be useful in the treatment of PD.

Neuroprotective effect of diclofenac on chlorpromazine induced catalepsy in rats.

Neuroinflammation plays a key role in progressive degeneration of dopaminergic cells. Upregulation of prostaglandins and free radicals formation are involved in the mechanisms of cell death in Parkinson's disease (PD). The present study aimed to investigate the neuroprotective effect of diclofenac against chlorpromazine (CPZ) induced catalepsy and motor impairment in mice. Adult Wistar rats treated with CPZ (3mg/kg/day, IP) were orally dosed with diclofenac and L-dopa/carbidopa for 21days. Catalepsy was measured after 21days of dosing by using standard bar test at 30, 60, 90, 120 and 180min then motor performances were assessed via open field test and wire hanging test. Histopathological investigation and determination of dopamine (DA) and 3,4-Dihydroxyphenylacetic acid (DOPAC) levels of rat's brain was also carried out. We found that CPZ treated group exhibited reduced motor impairment after 21days of treatment in open field and wire hanging test (P < 0.01) as compared to control group. The cataleptic scores of CPZ treated rats were also significantly increased (P < 0.01) after 21days of chronic dosing, however diclofenac treated groups showed significant reduction in cataleptic scores with improved motor performances. Histopathology of CPZ treated rats showed marked degeneration with architecture distortion in the mid brain region. Dopaminergic degeneration is confirmed by neurochemical results that showed reduced amount of dopamine and DOPAC levels in mid brain. Moreover, histopathological slides of diclofenac treated rats showed improved architecture with reduced gliosis of mid brain region as well as improved dopamine and DOPAC levels were achieved after 21days dosing of diclofenac. Taken together, the present work provide an evidence that diclofenac ameliorated behavioral performances by mediating neuroprotection against CPZ induced PD via preventing dopaminergic neuronal cell death.

Neonatal finasteride administration decreases dopamine release in nucleus accumbens after alcohol and food presentation in adult male rats

Endogenous levels of the neurosteroid (NS) allopregnanolone (AlloP) during neonatal stages are crucial for the correct development of the central nervous system (CNS). In a recent work we reported that the neonatal administration of AlloP or finasteride (Finas), an inhibitor of the enzyme 5α-reductase needed for AlloP synthesis, altered the voluntary consumption of ethanol and the ventrostriatal dopamine (DA) levels in adulthood, suggesting that neonatal NS manipulations can increase alcohol abuse vulnerability in adulthood. Moreover, other authors have associated neonatal NS alterations with diverse dopaminergic (DAergic) alterations. Thus, the aim of the present work is to analyse if manipulations of neonatal AlloP alter the DAergic response in the nucleus accumbens (NAcc) during alcohol intake in rats. We administered AlloP or Finas from postnatal day (PND) 5 to PND9. At PND98, we measured alcohol consumption using a two-bottle free-choice model (ethanol 10% (v/v)+glucose 3% (w/v), and glucose 3% (w/v)) for 12 days. On the last day of consumption, we measured the DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in NAcc in response to ethanol intake. The samples were obtained by means of in vivo microdialysis in freely moving rats, and DA and DOPAC levels were determined by means of high-performance liquid chromatography analysis (HPLC). The results revealed that neonatal Finas increased ethanol consumption in some days of the consumption phase, and decreased the DA release in the NAcc in response to solutions (ethanol+glucose) and food presentation. Taken together, these results suggest that neonatal NS alterations can affect alcohol rewarding properties.

Elevated dopamine concentration in light-adapted zebrafish retinas is correlated with increased dopamine synthesis and metabolism.

Probing zebrafish (Danio rerio) retinal cryostat sections, collected either 8h into the light or dark cycle, with an antibody against tyrosine hydroxylase (TH) identified a single population of immunopositive cells in the inner retina. However, the observed labeling patterns were not identical in both sets of tissues - label intensity was brighter in light-adapted tissue. This difference was quantified by probing western blots of retinal homogenates with the same TH antibody, which showed that TH expression increased by 42% in light-adapted tissue. High-performance liquid chromatography with electrochemical detection revealed that the concentrations of both dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) are also elevated in light-adapted zebrafish retinal tissue. Dopamine levels increased by 14% and DOPAC levels increased by 25% when measured in retinal homogenates harvested during the light cycle. These results indicate that dopamine levels in zebrafish retina are significantly increased in light-adapted tissue. The increase in dopamine content is correlated with an increase in both TH and DOPAC, suggesting that changes in dopamine concentration are due to light-adaptive changes in the synthesis, release and metabolism of dopamine. Dopamine concentration is elevated in lighted-adapted zebrafish retinas. This increase is correlated with an increase in both tyrosine hydroxylase (TH) and DOPAC (3,4-dihydroxyphenylacetic acid), suggesting that changes in dopamine concentration are due to light-adaptive changes in the synthesis, release and metabolism of dopamine. This is applicable to studies examining retinal mutants, the role of dopamine in disease or visual system development.

Long-Term Exposure to Paraquat Alters Behavioral Parameters and Dopamine Levels in Adult Zebrafish (Danio Rerio)

Chronic exposure to paraquat (Pq), a toxic herbicide, can result in Parkinsonian symptoms. This study evaluated the effect of the systemic administration of Pq on locomotion, learning and memory, social interaction, tyrosine hydroxylase (TH) expression, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels, and dopamine transporter (DAT) gene expression in zebrafish. Adult zebrafish received an i.p. injection of either 10 mg/kg (Pq10) or 20 mg/kg (Pq20) of Pq every 3 days for a total of six injections. Locomotion and distance traveled decreased at 24 h after each injection in both treatment doses. In addition, both Pq10- and Pq20-treated animals exhibited differential effects on the absolute turn angle. Nonmotor behaviors were also evaluated, and no changes were observed in anxiety-related behaviors or social interactions in Pq-treated zebrafish. However, Pq-treated animals demonstrated impaired acquisition and consolidation of spatial memory in the Y-maze task. Interestingly, dopamine levels increased while DOPAC levels decreased in the zebrafish brain after both treatments. However, DAT expression decreased in the Pq10-treated group, and there was no change in the Pq20-treated group. The amount of TH protein showed no significant difference in the treated group. Our study establishes a new model to study Parkinson-associated symptoms in zebrafish that have been chronically treated with Pq.

Parity decreases methamphetamine-induced striatal dopaminergic perturbation

The role of parity upon methamphetamine-induced neurotoxicity of the striatal dopaminergic system was assessed. Female CD-1 mice either remained nulliparous or underwent one or three complete pregnancies and were designated as the 0, 1 or 3 pregnancy groups. The mice were then treated with a neurotoxic regimen of methamphetamine (MA – 40mg/kg) or its saline vehicle (control) and striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured at 7-days post-MA. Basal levels of striatal DA, DOPAC and the DOPAC/DA ratio were similar among the saline (control) 0, 1 and 3 pregnancy groups. In response to MA, striatal DA and DOPAC were significantly decreased in the 0 and 1 pregnancy as compared with the control group. Mice with 3 pregnancies showed DA and DOPAC levels that did not differ from controls and were significantly greater than the 0 pregnancy group. The DOPAC/DA ratios of the 0 pregnancy group were significantly greater than all other groups (control, 1 and 3 pregnancy) which failed to differ among each other. These results demonstrate that parity decreases MA-induced striatal dopaminergic neurotoxicity, and the degree of this neuroprotection is related to the number of pregnancies experienced.

The impact of the hormonal milieu and stress-associated hypothalamic dopaminergic activation on the rapid compensatory adrenal growth in cycling female rats

We sought to investigate the impact of emotional and surgical stress applied in two hormonally different estrous-cycle phases as well as the hypothalamic dopaminergic involvement on the rapid compensatory adrenal growth (CAG) and the individual adrenal growth (IAG) in rats. After surgery for left and sham adrenalectomy (Adx) carried out on either diestrus-2 (DE-2) or proestrus (PE), CAG and IAG were evaluated in PE or estrus (E), respectively. Hypothalamic dopaminergic activity was also assessed by measuring dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in DE-2, PE and E in controls and in PE and E in sham and left adrenalectomized rats. All groups experienced similar chronic emotional stress assessed by the emotional reactivity score recorded during vaginal screening. In controls, DOPAC levels in DE-2 were higher than in PE and E. In PE, following surgery in DE-2, DOPAC levels and DOPAC/DA ratio were increased compared to PE controls; CAG was not significant, while negative correlations of IAG and CAG with DOPAC/DA ratio were observed. In E, CAG and IAG were significant, while dopaminergic activity was not increased compared to E controls. The significant CAG and IAG following left Adx in PE but not in DE-2 suggest a pronounced positive impact of the hormonal milieu on this process. The profound attenuation of CAG and IAG in PE suggests a negative effect of stress-associated dopaminergic activation.

Long-Term Consequences of Methamphetamine Exposure in Young Adults Are Exacerbated in Glial Cell Line-Derived Neurotrophic Factor Heterozygous Mice

Methamphetamine abuse in young adults has long-term deleterious effects on brain function that are associated with damage to monoaminergic neurons. Administration of glial cell line-derived neurotrophic factor (GDNF) protects dopamine neurons from the toxic effects of methamphetamine in animal models. Therefore, we hypothesized that a partial GDNF gene deletion would increase the susceptibility of mice to methamphetamine neurotoxicity during young adulthood and possibly increase age-related deterioration of behavior and dopamine function. Two weeks after a methamphetamine binge (4 x 10 mg/kg, i.p., at 2 h intervals), GDNF(+/-) mice had a significantly greater reduction of tyrosine hydroxylase immunoreactivity in the medial striatum, a proportionally greater depletion of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the striatum, and a greater increase in activated microglia in the substantia nigra than wild-type mice. At 12 months of age, methamphetamine-treated GDNF(+/-) mice exhibited less motor activity and lower levels of tyrosine hydroxylase-immunoreactivity, dopamine, DOPAC, and serotonin than wild-type mice. Greater striatal dopamine transporter activity in GDNF(+/-) mice may underlie their differential response to methamphetamine. These data suggest the possibility that methamphetamine use in young adults, when combined with lower levels of GDNF throughout life, may precipitate the appearance of parkinsonian-like behaviors during aging.

Effect of one-week ethanol treatment on monoamine levels and dopaminergic receptors in rat striatum.

We studied the effects of ethanol on the levels of norepinephrine, dopamine, serotonin (5-HT) and their metabolites as well as on D1- and D2-like receptors in the rat striatum. Ethanol (2 or 4 g/kg, po) was administered daily by gavage to male Wistar rats and on the 7th day, 30 min or 48 h after drug administration, the striatum was dissected for biochemical assays. Monoamine and metabolite concentrations were measured by HPLC and D1- and D2-like receptor densities were determined by binding assays. Scatchard analyses showed decreases of 30 and 43%, respectively, in D1- and D2-like receptor densities and no change in dissociation constants (Kd) 48 h after the withdrawal of the dose of 4 g/kg. Ethanol, 2 g/kg, was effective only on the density of D2-like receptors but not on Kd of either receptor. Thirty minutes after the last ethanol injection (4 g/kg), decreases of D2 receptor density (45%) as well as of Kd values (34%) were detected. However, there was no significant effect on D1-like receptor density and a 46% decrease was observed in Kd. An increase in dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), a decrease in norepinephrine, and no alteration in 5-HT levels were demonstrated after 48-h withdrawal of 4 g/kg ethanol. Similar effects were observed in dopamine and DOPAC levels 30 min after drug administration. No alteration in norepinephrine concentration and a decrease in 5-HT levels were seen 30 min after ethanol (4 g/kg) administration. Our findings indicate the involvement of the monoaminergic system in the responses to ethanol.

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.

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.

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.

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.

Effect of 6-hydroxydopamine lesions of the medial prefrontal cortex on intravenous cocaine self-administration under a progressive ratio schedule of reinforcement

Rats were trained to self-administer intravenous cocaine under a progressive ratio (PR) schedule of reinforcement. Under this schedule, an increasing number of lever responses had to be made to obtain each subsequent reinforcement (1.5 mg/kg per injection). Once stable responding was achieved with this schedule, bilateral 6-hydroxydopamine (6-OHDA) or vehicle-only injections were delivered into the medial prefrontal cortex (mPFC). Following recovery from surgery, the animals were given access to cocaine under the PR schedule. The effect of the lesion on self-administration behaviour was examined at various doses of cocaine (0.09–1.5 mg/kg per injection). 6-OHDA lesions of the mPFC had no effect on self-administration behaviour at the higher unit doses of cocaine. However, at the lower doses (0.09 and 0.19 mg/kg per injection), the lesion caused a significant increase in break point (BP), the number of responses made to obtain the last reinforcement of a self-administration session. The neurochemical results showed a significant reduction (57%) in mPFC levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) (53%), with no changes in noradrenaline or serotonin levels. In contrast, the lesion caused no changes in DA or DOPAC levels in the nucleus accumbens (NACC) or striatum. These results indicate that the DAergic innervation of the mPFC cortex has a role in cocaine self-administration behaviour; however, whether this role is contingent on NACC DA function remains to be elucidated.

Daily variation in the content of indoleamines, catecholamines and related compounds in the pineal gland of Syrian hamsters kept under long and short photoperiods.

This study examined the diurnal changes in the content of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), N-acetylserotonin (NAS), melatonin, 5-methoxytryptophol (5-ML), noradrenaline (NA), dopamine (DA), and 3, 4-dihydroxyphenylacetic acid (DOPAC) in the pineal gland of Syrian hamsters kept under long (14L:10D) and short (10L:14D) photoperiods. The nocturnal increase in NAS and melatonin levels was dependent upon the prevailing photoperiod, with a prolonged duration when the night lengthened. In both photoperiods, NAS and melatonin contents increased several hours after the onset of darkness, and, in animals kept in short photoperiod, the levels of both compounds began to decrease before light onset. On the contrary, decreases were noted in 5-HT, 5-HIAA, and 5-ML contents during the night, which was directly proportional to the dark phase. 5-HTP levels did not show a rhythmic variation. Correlations between the mean values of 5-HT-related compounds showing daily rhythms were very high when group means were compared, but they decreased when values from individual animals were considered. In addition, when correlations were calculated on per-animal basis during the night phase, a weak negative correlation was found for 5-HT vs NAS and 5-HT vs melatonin, although the correlation of 5-HT with positively 5-HT-correlated compounds (5-HIAA and 5-ML) continued to be high. These results indicate that the nocturnal increase in the N-acetyl transferase activity is the major factor generating the rhythm of pineal 5-HT content, but that other photoperiod-dependent mechanisms (i.e., 5-HT synthesis or release) seem to be also implicated. On the other hand, this study shows that NA content in the Syrian hamster pineal gland does not exhibit daily variations, although marked nocturnal increases in the levels of DA and DOPAC were evident. These results suggest the existence of parallel daily alterations in pineal catecholamine synthesis and release, and suggest a role for DA in the pineal activation at night.