Plasma Dopamine Research Articles

Relative Efficiencies of Plasma Catechol Levels and Ratios for Neonatal Diagnosis of Menkes Disease

Menkes disease is an X-linked recessive neurodevelopmental disorder resulting from mutation in a copper-transporting ATPase gene. Menkes disease can be detected by relatively high concentrations of dopamine (DA) and its metabolites compared to norepinephrine (NE) and its metabolites, presumably because dopamine-beta-hydroxylase (DBH) requires copper as a co-factor. The relative diagnostic efficiencies of levels of catechol analytes, alone or in combination, in neonates at genetic risk of Menkes disease have been unknown. Plasma from 44 at-risk neonates less than 30 days old were assayed for DA, NE, and other catechols. Of the 44, 19 were diagnosed subsequently with Menkes disease, and 25 were unaffected. Compared to unaffected at-risk infants, those with Menkes disease had high plasma DA (P < 10(-6)) and low NE (P < 10(-6)) levels. Considered alone, neither DA nor NE levels had perfect sensitivity, whereas the ratio of DA:NE was higher in all affected than in all unaffected subjects (P = 2 x 10(-8)). Analogously, levels of the DA metabolite, dihydroxyphenylacetic acid (DOPAC), and the NE metabolite, dihydroxyphenylglycol (DHPG), were imperfectly sensitive, whereas the DOPAC:DHPG ratio was higher in all affected than in all unaffected subjects (P = 2 x 10(-4)). Plasma dihydroxyphenylalanine (DOPA) and the ratio of epinephrine (EPI):NE levels were higher in affected than in unaffected neonates (P = 0.0015; P = 0.013). Plasma DA:NE and DOPAC:DHPG ratios are remarkably sensitive and specific for diagnosing Menkes disease in at-risk newborns. Affected newborns also have elevated DOPA and EPI:NE ratios, which decreased DBH activity alone cannot explain.

Normal plasma dopamine-beta-hydroxylase in non-treated and treated Parkinson patients.

Plasma dopamine-beta-hydroxylase activity (DBH) was estimated in 50 drug-free Parkinson patients, 30 of whom had never been treated, in 26 patients treated chronically with L-Dopa, and in 44 controls. 22 of the drug-free patients were examined again after two weeks treatment with L-Dopa plus decarboxylase inhibitor. In disagreement with other reports, no differences were found among the groups and no change in the enzyme activity occurred after treatment, although urinary homovanillic acid increased 20 fold. Low DBH activities could not be attributed to the age of onset or duration of illness, main symptom, depression, autonomic disturbances, or duration of drug treatment. The only difference was found in patients with dementia associated to their illness, who showed low enzyme activities.

Quantitative and qualitative profiling of endocannabinoids in human plasma using a triple quadrupole linear ion trap mass spectrometer with liquid chromatography

Owing to the large implication of endocannabinoids (ECs) in many physiological and pathophysiological processes, a rapid liquid chromatography/electrospray ionisation triple quadrupole linear ion trap mass spectrometric assay (LC/ESI-QqQ(LIT)) was developed for the detection and characterization of anandamide (AEA), 2-arachidonoyl glycerol (2-AG), virodhamine (VA), noladin ether (2-AGE), and N-arachidonoyl dopamine (NADA) in human plasma. The ECs were extracted from 500 microL of plasma by liquid-liquid extraction (LLE) and separated by using an XTerra C18 MS column (50 x 3.0 mm i.d., 3.5 microm) with gradient elution. The mobile phase was composed of a mixture of acetonitrile, water, and formic acid (0.1%). For confirmatory analysis, an information-dependent acquisition (IDA) experiment was performed with selected reaction monitoring (SRM) as survey scan and enhanced product ion (EPI) as dependent scan. The assay was found to be linear in the concentration range of 0.1-5 ng/mL for AEA, 0.3-5 ng/mL for VA, 2-AGE, and NADA and 1-20 ng/mL for 2-AG using a 0.5 mL aliquot of plasma. Repeatability and intermediate precision were found less than 15% over the tested concentration ranges. The developed method thus provided the rapid, highly sensitive and highly selective requirement for assess quantitation, and identification of ECs in plasma.

Comparison of the effect of anti-muscarinic agents on bladder activity, urinary ATP level, and autonomic nervous system in rats

We compared the effect of 4 anti-muscarinic agents on bladder activity, urinary ATP levels, and autonomic nervous system in rats. Rats were divided into the following 5 groups (control group, oxybutynin group, propiverine group, tolterodine group, imidafenacin group), and were administered daily the designated anti-muscarinic agent or distilled water into the stomach. After 2 weeks, we performed 1) continuous cystometry with physiological saline and 0.1% acetic acid solution, 2) measurement of urinary ATP level before and after bladder stimulation, and 3) measurement of the heart rate, blood pressure and plasma catecholamines. The maximum bladder contraction pressure increased and the interval between contractions became shorter during cystometry with acetic acid solution in the control group, but not in the 4 anti-muscarinic agent groups. The urinary ATP level increased after bladder stimulation in all groups, but the increase was smaller in the propiverine and imidafenacin groups. The plasma noradrenaline and dopamine levels of the propiverine group were higher. Taken together, all anti-muscarinic agents inhibited the bladder activity without changing the heart rate and blood pressure. Especially, the inhibitory effect of propiverine and imidafenacin on bladder activity may be partly due to blocking an increase of ATP release from the bladder urothelium.

Codrugs Linking l-Dopa and Sulfur-Containing Antioxidants: New Pharmacological Tools against Parkinson’s Disease

A series of multifunctional codrugs (1-6) were synthesized to overcome the pro-oxidant effect associated with L-dopa (LD) therapy. Target compounds release LD and dopamine (DA) in human plasma after enzymatic hydrolysis, displaying an antioxidant effect superior to that of N-acetylcysteine (NAC). After intracerebroventricular injection of codrug 4, the levels of DA in the striatum were higher than those in LD-treated groups, indicating that this compound has a longer half-life in brain than LD.

Levels of Catecholamines, Arginine Vasopressin and Atrial Natriuretic Peptide in Hypotensive Extremely Low Birth Weight Infants in the First 24 Hours after Birth

Background: Extremely low birth weight infants (ELBWI) often suffer from severe hypotension in the early neonatal period. However, few previous studies have ever revealed plasma levels of vasoactive substances which regulate the cardiovascular system in ELBWI. Objective: To study plasma levels of vasoactive substances in ELBWI with hypotension during the first 24 h of life. Methods: 22 ELBWI with hypotension (gestational age 26.4 ± 1.9 weeks; birth weight 751 ± 135 g) were involved in the study. After initial volume therapy, the infants were arbitrarily divided into two groups depending on requirement of dopamine dosage: severe hypotension group (SH; dopamine >10 μg/kg/min, n = 9) and mild hypotension group (MH; dopamine ≤10 μg/kg/min, n = 13). Plasma levels of dopamine, norepinephrine, epinephrine, arginine vasopressin, and atrial natriuretic peptide were measured at admission and at 24 h after birth. Results: Infants in the SH group had higher plasma dopamine than infants in the MH group both at admission (median; range: 14,410; 224–46,770 vs. 7,900; 32–21,220 pg/ml, p < 0.05) and at 24 h (80,920; 494–146,100 vs. 25,680; 10,130–63,180 pg/ml; p < 0.05). The norepinephrine/dopamine ratio (median; range) was lower in the SH group than in the MH group at admission (0.3; 0.0–1.0 vs. 1.1; 0.1–25.1; p < 0.01). Plasma levels of atrial natriuretic peptide or arginine vasopressin were not different between the two groups. Conclusions: ELBWI with SH may have decreased conversion of dopamine to norepinephrine. We speculate that this mechanism may contribute to development of SH in ELBWI.

Neuronal Source of Plasma Dopamine

Determinants of plasma norepinephrine (NE) and epinephrine concentrations are well known; those of the third endogenous catecholamine, dopamine (DA), remain poorly understood. We tested in humans whether DA enters the plasma after corelease with NE during exocytosis from sympathetic noradrenergic nerves. We reviewed plasma catecholamine data from patients referred for autonomic testing and control subjects under the following experimental conditions: during supine rest and in response to orthostasis; intravenous yohimbine (YOH), isoproterenol (ISO), or glucagon (GLU), which augment exocytotic release of NE from sympathetic nerves; intravenous trimethaphan (TRI) or pentolinium (PEN), which decrease exocytotic NE release; or intravenous tyramine (TYR), which releases NE by nonexocytotic means. We included groups of patients with pure autonomic failure (PAF), bilateral thoracic sympathectomies (SNS-x), or multiple system atrophy (MSA), since PAF and SNS-x are associated with noradrenergic denervation and MSA is not. Orthostasis, YOH, ISO, and TYR increased and TRI/PEN decreased plasma DA concentrations. Individual values for changes in plasma DA concentrations correlated positively with changes in NE in response to orthostasis (r = 0.72, P < 0.0001), YOH (r = 0.75, P < 0.0001), ISO (r = 0.71, P < 0.0001), GLU (r = 0.47, P = 0.01), and TYR (r = 0.67, P < 0.0001). PAF and SNS-x patients had low plasma DA concentrations. We estimated that DA constitutes 2%-4% of the catecholamine released by exocytosis from sympathetic nerves and that 50%-90% of plasma DA has a sympathoneural source. Plasma DA is derived substantially from sympathetic noradrenergic nerves.

Mucuna pruriens improves male fertility by its action on the hypothalamus–pituitary–gonadal axis

To understand the mechanism of action of Mucuna pruriens in the treatment of male infertility. Prospective study. Departments of Biochemistry, Urology, and Obstetrics and Gynecology, C.S.M. Medical University, Lucknow, India. Seventy-five normal healthy fertile men (controls) and 75 men undergoing infertility screening. High-performance liquid chromatography assay for quantitation of dopa, adrenaline, and noradrenaline in seminal plasma and blood. Estimation by RIA of hormonal parameters in blood plasma, namely T, LH, FSH, and PRL. Before and after treatment, serum T, LH, FSH, PRL, dopamine, adrenaline, and noradrenaline in seminal and blood plasma were measured. Decreased sperm count and motility were seen in infertile subjects. Serum T and LH levels, as well as seminal plasma and blood levels of dopamine, adrenaline, and noradrenaline were also decreased in all groups of infertile men. This was accompanied by significantly increased serum FSH and PRL levels in oligozoospermic subjects. Treatment with M. pruriens significantly improved T, LH, dopamine, adrenaline, and noradrenaline levels in infertile men and reduced levels of FSH and PRL. Sperm count and motility were significantly recovered in infertile men after treatment. Treatment with M. pruriens regulates steroidogenesis and improves semen quality in infertile men.

Appearance Matters: Artificial Marking Alters Aggression and Stress

Artificial marking of animals for identification is frequently employed by researchers in the behavioral, biomedical, agricultural, and environmental sciences. The impact of artificial marking on experimental results is rarely explicitly considered despite evidence demonstrating that changes in phenotypic appearance can modify animal behavior and reproductive success. Here we present evidence that artificial marking of individuals within a social group has frequency-dependent effects on the behavior and physiology of domestic fowl (Gallus gallus domesticus). We demonstrate that when only 20 or 50% of individuals within a group were artificially marked, the marked birds received more aggression and had lesser body mass than the unmarked individuals within the same group. Furthermore, in groups in which only a small proportion of the individuals were marked, we report altered plasma epinephrine and dopamine levels in marked individuals. These effects of marking were imperceptible when all birds in a group were marked. This finding has important implications for animal research because, when only a subset of group members is artificially marked and used for data collection, the results obtained may not be representative of the population.

Function of Tongue-Playing of Cattle in Association With Other Behavioral and Physiological Characteristics

To study the function of tongue-playing of cattle, this study observed 71 Japanese Black × Holstein steers after feeding in 2 repetitive experiments. The number of steers who performed tongue-playing did not differ among the 3 levels of environmentally enriched pens. Most (90.6%) performances of tongue-playing terminated within 20 min. Frequency of tongue-playing positively correlated with the frequency of resting (r = 0.25, p < .05). Frequency of eating was lower in tongue-playing steers (n = 40) than in non-tongue-playing steers (n = 31; p < .05). Frequencies of self-grooming (p < .05), ruminating (p < .05), and lying ruminating (p < .01) were higher in tongue-playing steers. Plasma dopamine concentration was lower in tongue-playing steers (p < .05). In conclusion, tongue-playing that lasts only for a short time after feeding was induced by behavioral features of steers who rest more and eat hay less at the same time as they perform grooming and ruminating.

Seasonal Changes in Circadian Peripheral Plasma Concentrations of Melatonin, Serotonin, Dopamine and Cortisol in Aged Horses with Cushing’s Disease under Natural Photoperiod

Equine pituitary pars intermedia dysfunction (PPID) is a common and serious condition that gives rise to Cushing’s disease. In the older horse, it results in hyperadrenocorticism and disrupted energy metabolism, the severity of which varies with the time of year. To gain insight into the mechanism of its pathogenesis, 24-h profiles for peripheral plasma melatonin, serotonin, dopamine and cortisol concentrations were determined at the winter and summer solstices, and the autumn and spring equinoxes in six horses diagnosed with Cushing’s disease and six matched controls. The nocturnal rises in plasma melatonin concentrations, although different across seasons, were broadly of the same duration and similar amplitude in both groups of animals (P > 0.05). The plasma concentrations of cortisol did not show seasonal variation and were different in diseased horses only in the summer when they were higher across the entire 24-h period (P < 0.05). Serotonin concentrations were not significantly affected by time of year but tended to be lower in Cushingoid horses (P = 0.07). By contrast, dopamine output showed seasonal variation and was significantly lower in the Cushing’s group in the summer and autumn (P < 0.05). The finding that the profiles of circulating melatonin are similar in Cushingoid and control horses reveals that the inability to read time of year by animals suffering from Cushing’s syndrome is an unlikely reason for the disease. In addition, the results provide evidence that alterations in the dopaminergic and serotoninergic systems may participate in the pathogenesis of PPID.

Vasoconstrictor-induced hypertension following multiple blood transfusions in children with congenital hemolytic anemia.

Introduction. The mechanism by which blood transfusion increases blood pressure in a substantial proportion of patients with congenital hemolytic anemia is unknown. Vascular endothelium dysfunction and increased endogenous vasoactive substances have been postulated in the pathogenesis of hypertension following multiple blood transfusions. The present study was undertaken to test the hypothesis whether increased circulating vasoconstrictors following blood transfusions, if documented, is a potent modulator of hypertension in patients with congenital anemia. Materials and Methods. Four children with congenital hemolytic anemia developed severe hypertension and convulsions 2 to 4 days after they received multiple blood transfusions. None had a history of prior hypertension, kidney disease or seizures before the blood transfusion. Baseline blood and urine samples were obtained for routine renal function studies. Blood samples were also drawn during and 2 weeks after the clinical events for determination of epinephrine, norepinephrine, dopamine, and plasma renin activity. Results. Kidney function was normal in all the 4 patients. All had elevated plasma renin activity and increased blood epinephrine, norepinephrine, and dopamine concentrations during hypertensive crises. Hypertension responded to antihypertensive drugs with the patients remaining normotensive 3 to 6 days after commencing therapy. All recovered without further seizures. The elevated plasma renin activity, epinephrine, norepinephrine, and dopamine levels returned to reference levels 2 weeks after completion of the last blood transfusion. Conclusions. These data suggest that increased activity of vasoconstrictors in the recipient plasma may be responsible for the development of hypertension after multiple blood transfusions.

Arginine-induced pancreatitis: involvement of the autonomic nervous system?

to the editor: Dawra et al. ([1][1]) were able to trigger acute pancreatitis in mice after the administration of l-arginine. In addition, acute inflammation in the pancreas was associated with lung injury. With respect to this, we would like to offer some insight into the possible physiological,

Reduced tumor growth in a mouse model of schizophrenia, lacking the dopamine transporter

The incidence of cancer in patients with schizophrenia has been reported to be lower that in the general population. On the other hand, it is well established that patients with schizophrenia have a hyper-dopaminergic system and dopamine has the ability to inhibit tumor angiogenesis. Therefore, in order to investigate the molecular mechanisms responsible for the lower cancer risk in schizophrenic patients, we used a mouse model of schizophrenia, which shows hyper-dopaminergic transmission in the nerve terminals of dopaminergic neurons. Here, we hypothesized that tumor growth was reduced in a mouse model of schizophrenia, lacking the dopamine transporter (DAT), and investigated tumor growth and angiogenesis in DAT knockout mice. The subcutaneous tumor in mice inoculated with cancer cells was smaller in DAT-/- mice than in the wild type (p < 0.05); however, the level of plasma dopamine in DAT-/- mice was lower than that of control littermates. Using human umbilical vascular endothelial cells (HUVEC), we examined dopamine signaling through dopamine D(1) receptor (D(1)R) and D(2)R. Dopamine stimulation slightly decreased the surface expression of vascular endothelial growth factor receptor-2 (VEGF-R2) but induced the phosphorylation of VEGF-R2 through Src in HUVEC. In addition, DAT-/- mice had less D(1)R. Both pharmacological and genetic interruption of D(1)R showed inhibited tumor growth. These results suggest that modulation of the dopaminergic system may contribute to cancer therapy.

Effect of clonidine on plasma-catecholamine levels at rest and on ergometric exercise (author's transl)

The effect of clonidine on peripheral venous-plasma catecholamine concentration was assessed in ten subjects with normal circulation, at rest and on submaximal bicycle exercise. Three hours after oral intake of 300 micrograms clonidine in single dose there was significant lowering of the plasma adrenaline and noradrenaline levels. Six hours after intake the lowest plasma catecholamine level was reached, but after 24 hours the clonidine effect had largely disappeared. The sympatholytic effect of clonidine was relatively less marked with bicycle exercise than at rest. When clonidine had been given for only a short period at moderate dosage, there was no exaggerated catecholamine rise. Clonidine administration did not effect plasma dopamine levels. These results indicate that clonidine decreases plasma adrenaline and noradrenaline levels without significant effect on circulatory regulation.

Neonatal Diagnosis and Treatment of Menkes Disease

Menkes disease is a fatal neurodegenerative disorder of infancy caused by diverse mutations in a copper-transport gene, ATP7A. Early treatment with copper injections may prevent death and illness, but presymptomatic detection is hindered by the inadequate sensitivity and specificity of diagnostic tests. Exploiting the deficiency of a copper enzyme, dopamine-beta-hydroxylase, we prospectively evaluated the diagnostic usefulness of plasma neurochemical levels, assessed the clinical effect of early detection, and investigated the molecular bases for treatment outcomes. Between May 1997 and July 2005, we measured plasma dopamine, norepinephrine, dihydroxyphenylacetic acid, and dihydroxyphenylglycol in 81 infants at risk. In 12 newborns who met the eligibility criteria and began copper-replacement therapy within 22 days after birth, we tracked survival and neurodevelopment longitudinally for 1.5 to 8 years. We characterized ATP7A mutations using yeast complementation, reverse-transcriptase-polymerase-chain-reaction analysis, and immunohistochemical analysis. Of 81 infants at risk, 46 had abnormal neurochemical findings indicating low dopamine-beta-hydroxylase activity. On the basis of longitudinal follow-up, patients were classified as affected or unaffected by Menkes disease, and the neurochemical profiles were shown to have high sensitivity and specificity for detecting disease. Among 12 newborns with positive screening tests who were treated early with copper, survival at a median follow-up of 4.6 years was 92%, as compared with 13% at a median follow-up of 1.8 years for a historical control group of 15 late-diagnosis and late-treatment patients. Two of the 12 patients had normal neurodevelopment and brain myelination; 1 of these patients had a mutation that complemented a Saccharomyces cerevisiae copper-transport mutation, indicating partial ATPase activity, and the other had a mutation that allowed some correct ATP7A splicing. Neonatal diagnosis of Menkes disease by plasma neurochemical measurements and early treatment with copper may improve clinical outcomes. Affected newborns who have mutations that do not completely abrogate ATP7A function may be especially responsive to early copper treatment. (ClinicalTrials.gov number, NCT00001262.)

Plasma Dopamine, Norepinephrine, Epinephrine and DOPAC Levels in Preterm Infants Prior to and Immediately after a Sleep Ventilation Hypercarbia Test

The postnatal maturation and the adaptational ability of the sympathoadrenal system has been investigated in preterm neonates (n = 8), and in sick preterm neonates with respiratory disorders (n = 10). Plasma levels of dopamine (DA), norepinephrine (NE), epinephrine (E) and 3-4 dihydroxyphenylacetic acid (DOPAC) were evaluated at rest during the first month of life, and following an inhalation of a 5% carbon dioxide-21% oxygen mixture for 10 min. During the first month of life the sick preterm neonates exhibited similar NE, E, and DOPAC plasma levels but higher DA amounts than healthy infants. Plasma DA levels were inversely correlated with the transcutaneous oxygen tension (r = -0.636) indicating that hypoxemia was able to enhance the release of DA. Immediately following the hypercarbia test, there were no significant changes of plasma catecholamine levels in the sick preterms, but there was a significant increase of E plasma levels (+140%, p less than 0.05) and a moderate elevation of NE and DA amounts in the healthy preterms. It is concluded that preterm neonates who have had respiratory disorders did not exhibit an immaturity of the sympathoadrenal system at rest, but had a defect in the release of E following hypercarbia exposure, which may be secondary to an alteration in chemoreceptor function and/or reduced catecholamine stores.

Correlation of plasma dopamine beta-hydroxylase activity with polymorphisms in DBH gene: a study on Eastern Indian population.

Plasma dopamine beta-hydroxylase activity (plDbetaH) is tightly regulated by the DBH gene and several genetic polymorphisms have been found to independently exert their influence. In the present investigation, association of four DBH polymorphisms, DBH-STR, rs1611115, rs1108580, and rs2519152 with plDbetaH was examined in blood samples from 100 unrelated individuals belonging to the state of West Bengal, Eastern India. Genotypes obtained after PCR amplification and restriction digestion were used for statistical analyses. plDbetaH was measured using a photometric assay and its correlation with the genetic polymorphisms was analyzed using analysis of variance and linear regression. Moderate linkage disequilibrium (LD) was observed between DBH-STR and rs1611115, while rs1108580 and rs2519152 were in strong LD. 'T' allele of rs1611115 showed strong negative correlation with plDbetaH, whereas DBH-STR, rs1108580 and rs2519152 had no major effect. Four haplotypes showed significant influence on plDbetaH. This is the first report on the effect of genetic polymorphisms on plDbetaH from the Indian sub-continent. rs1611115 was the only polymorphism that showed substantial control over plDbetaH. Other polymorphisms which did not show individual effects could possibly be part of larger haplotype blocks that carry the functional polymorphisms controlling plDbetaH.

Effect of sildenafil (Viagra®) on the genital reflexes of paradoxical sleep-deprived male rats

Since there is evidence that paradoxical sleep deprivation (PSD) elicits penile erection (PE) and ejaculation (EJ), and that the erectile response of rats is mediated by nitric oxide, the present study sought to extend the latter finding by assessing the effects of sildenafil on the genital reflexes of male Wistar rats subjected to PSD. We also determined the influence of sildenafil on hormone concentrations. In the first experiment, sildenafil at doses ranging from 0.08 to 0.32 mg/kg was administered intraperitoneally to rats that had been deprived of sleep for 4 days and to home cage controls (N = 8-10/group). The frequency of PE and EJ was measured for 60 min. PSD alone induced PE in 50% of the animals; however, a single injection of sildenafil did not significantly increase the percentage of rats displaying PE compared to PSD-saline or to home cage groups. PSD alone also induced spontaneous EJ, but this response was not potentiated by sildenafil in the dose range tested. Testosterone concentrations were significantly lower in PSD rats (137 +/- 22 ng/dL) than in controls (365 +/- 38 ng/dL), whereas progesterone (0.9 +/- 0.1 vs 5.4 +/- 1 ng/mL) and plasma dopamine (103.4 +/- 30 vs 262.6 +/- 77 pg/mL) increased. These changes did not occur after sildenafil treatment. The data show that although sildenafil did not alter the frequency of genital reflexes, it antagonized hormonal (testosterone and progesterone) and plasma dopamine changes induced by PSD. The stimulation of the genital reflexes by sildenafil did not result in potentiating effects in PSD rats.

Effect of sildenafil (Viagra®) on the genital reflexes of paradoxical sleep-deprived male rats

Since there is evidence that paradoxical sleep deprivation (PSD) elicits penile erection (PE) and ejaculation (EJ), and that the erectile response of rats is mediated by nitric oxide, the present study sought to extend the latter finding by assessing the effects of sildenafil on the genital reflexes of male Wistar rats subjected to PSD. We also determined the influence of sildenafil on hormone concentrations. In the first experiment, sildenafil at doses ranging from 0.08 to 0.32 mg/kg was administered intraperitoneally to rats that had been deprived of sleep for 4 days and to home cage controls (N = 8-10/group). The frequency of PE and EJ was measured for 60 min. PSD alone induced PE in 50% of the animals; however, a single injection of sildenafil did not significantly increase the percentage of rats displaying PE compared to PSD-saline or to home cage groups. PSD alone also induced spontaneous EJ, but this response was not potentiated by sildenafil in the dose range tested. Testosterone concentrations were significantly lower in PSD rats (137 ± 22 ng/dL) than in controls (365 ± 38 ng/dL), whereas progesterone (0.9 ± 0.1 vs 5.4 ± 1 ng/mL) and plasma dopamine (103.4 ± 30 vs 262.6 ± 77 pg/mL) increased. These changes did not occur after sildenafil treatment. The data show that although sildenafil did not alter the frequency of genital reflexes, it antagonized hormonal (testosterone and progesterone) and plasma dopamine changes induced by PSD. The stimulation of the genital reflexes by sildenafil did not result in potentiating effects in PSD rats.