Rectal swab testing before prostate biopsy: experience in a VA Medical Center urology practice.

BACKGROUND: Infectious complications following transrectal ultrasound prostate biopsy (TRUSBx) have been increasing. Pre-biopsy prophylaxis with fluoroquinolone (FQL) antibiotics is a recommended and accepted practice. Increasing emergence of FQL-resistant bacteria is believed to be related to the increase in infectious complications. We sought to determine the effect of targeted antibiotic prophylaxis (TAP) before TRUSBx on infectious complications in our practice. METHODS: TAP was introduced in our practice in 2012. A retrospective analysis was performed analyzing infectious complications from TRUSBx before and after TAP was introduced. Two hundred forty-four patients underwent TRUSBx with TAP directed by bacterial antibiotic sensitivity identified on rectal swab. A group of two hundred sixty-four consecutive patients who underwent TRUSBx in our practice before introduction of TAP were chosen for comparison. Infectious complications were recorded and compared between groups. Prostate volume, PSA, number of biopsy cores, finding of prostate cancer, presence of diabetes, race and age were also compared. RESULTS: The infectious complication rate after TRUSBx in the pre-TAP group was 7/264 (2.65%), the rate in the TAP group was 1/244 (0.41%), a statistically significant difference (P=<0.05). There were no differences between groups in regards to prostate volume, number of prostate biopsy cores, race and presence of diabetes. The rectal swab group was younger (65.4 ± 6.0) than the non-swab group (67.9 ± 6.2), had higher PSA values, and a higher chance of prostate cancer on biopsy. CONCLUSIONS: The use of TAP based on rectal swab testing significantly lowered our infectious complication rate for TRUSBx. TAP is now adopted as standard practice before TRUSBx in our center. The younger age and higher chance of prostate cancer on biopsy in the rectal swab group, we believe, is due to implementation of recent guidelines directing urologists be more selective in recommending prostate biopsy to older men.

Niveles séricos del antígeno prostático específico (PSA) dentro de la campaña de prevención del cáncer de próstata / Serum levels of the prostate-specific antigen (PSA) in the prostate cancer prevention campaign

La determinación del antígeno prostático específico (PSA) forma parte del diagnóstico del cáncer de próstata. Como en condiciones patológicas sus niveles aumentan, es considerado marcador tumoral útil de diagnóstico de cáncer de próstata en forma precoz. Determinamos los niveles séricos de PSA, dentro de la campaña “Semana de la Próstata” organizado por la Cátedra de Urología del Hospital de Clínicas en Octubre 2007. De los 89 pacientes, el 86,5% presentó niveles de PSA entre 0 y 4ng/ml, 10,1% entre 4 y 10 ng/ml y el 3,4% entre 10 y 40 ng/ml respectivamente. Se realizó una distribución por edad y se determinaron las medias de los valores de PSA en los mismos. El 12,4% del grupo E1 (41 a 50 años) con 0,5ng/ml de PSA, el 52,8% del grupo E2 (51 a 60 años) con 7,4ng/ml de PSA, el 28,1% del grupo E3 (61 a 70 años) con 5,2ng/ml de PSA y el 6,7% del grupo E4 (71 a 80 años) con 1,5 ng/ml de PSA. Hallándose valores más elevados de PSA en el grupo E2 y E3, no así en el grupo E4. En relación al tacto rectal (TR) y los valores del PSA, el 31,5%(28) presentaron TR normal con un valor medio de PSA de 3,4. Mientras que el 65,1% (58) presentaban TR patológico con valores medios de PSA de 7,17 en 55 pacientes y sólo 3 pacientes con TR patológico presentaron niveles de PSA por debajo de 2,5 ng/ml. El TR resultó ser la variable con mayor poder de discriminación, con respecto al resultado de PSA en estos pacientes.

The determination of prostate-specific antigen (PSA) is part of the diagnosis of prostate cancer.It is considered an useful tumor marker for early diagnosis of porostate cancer because in pathological conditions its levels increase.Serum levels of PSA were determined within the campaign "Prostate Week" organized by the Department of Urology of the Hospital de Clínicas in October 2007.;Of the 89 patients, 86.5% had PSA levels between 0 and 4 ng/ml, 10.1% between 4 and 10 ng/ml and 3.4% between 10 and 40 ng/ml respectively. An age distribution was made and the mean of PSA values were determined in each group. Twelve point four percent of group E1 (41 to 50 years) had 0.5 ng/ml of PSA, 52.8% of group E2 (51 to 60 years) 7.4 ng/ml PSA, 28.1% of E3 group (61 to 70 years) 5.2 ng/ ml of PSA and 6.7% of the E4 group (71 to 80 years) had 1.5 ng/ml of PSA.The highest values of PSA were found in E2 and E3 groups, but not in the E4 group. In relation to digital rectal examination (DRE) and PSA values, 31.5% (28) showed normal DRE with a mean value of PSA of 3.4 while 65.1% (58) had pathological DRE with mean values of PSA of 7.17 in 55 patients and only 3 patients had pathological TR with PSA levels below 2.5 ng/ml. The DRE was the variable with the greatest ability to discriminate in relation to the results of PSA in these patients.

Macrophage migration inhibitory factor (MIF) gene polymorphisms are associated with increased prostate cancer incidence.

Recurrent or persistent inflammation has emerged as an important factor in cancer development. Overexpression of macrophage migration inhibitory factor (MIF), an upstream regulator of innate immunity with pleiotropic effects on cell proliferation, has been implicated in prostate cancer (CaP). Two polymorphisms in the promoter of the MIF gene (-173G to C transition and seven copies of the -794 CATT repeat) are associated with increased MIF expression in vivo and poor prognosis in autoimmune diseases. We conducted a retrospective analysis of 131 CaP patients and 128 controls from a group of Veterans' Administration patients undergoing routine prostate-specific antigen screening. Patients with CaP were enrolled regardless of treatment. Inclusion criteria for the control group were absence of documented diagnosis of cancer and/or chronic inflammation within patient computerized records. Logistic regression demonstrated a significant association between CaP and the -173G/C, the -173C/C and the -794 7-CATT MIF polymorphisms (P<0.001). Patients with the -794 7-CATT allele had an increased risk of CaP recurrence at 5 years. Individuals with -173G/C, -173C/C and -794 7-CATT MIF genotypes have an increased incidence of CaP and these genotypes may serve as an independent marker for cancer recurrence.

Effects of two atypical neuroleptics, olanzapine and risperidone, on the function of the urinary bladder and the external urethral sphincter in anesthetized rats.

BACKGROUND: A previous report showed that the atypical neuroleptic clozapine resulted in marked changes in urodynamic parameters and greatly inhibited the activity of the external urethral sphincter in anesthetized rats. Such findings may help explain the high incidence of urinary disturbances reported during clozapine therapy. In an effort to extend our observations to other atypical neuroleptic agents, the present study investigated the effects of two newer atypical antipsychotics, olanzapine and risperidone, on the bladder and external urethral sphincter during cystometry in anesthetized rats. RESULTS: At a dose of 0.1 mg/kg (i.v.), olanzapine decreased the micturition volume and increased the residual volume. In addition, olanzapine decreased the expulsion time and the amplitude of the high frequency oscillations observed during the expulsion phase. Larger doses (1 mg/kg) had a greater effect. Olanzapine also reduced the activity recorded from the external urethral sphincter, and the bursting observed during the expulsion phase was abolished by 1.0 mg/kg. Risperidone had similar effects although the maximal effects were smaller than those observed with olanzapine. The amplitude of bladder contractions elicited by electrical stimulation of the pelvic nerve was reduced by olanzapine but not risperidone suggesting a possible anti-muscarinic peripheral effect of olanzapine. CONCLUSIONS: Olanzapine and risperidone significantly altered several voiding parameters and decreased the activity of the external urethral sphincter in the anesthetized rat. We propose that these effects are due to the central action of these drugs and not to peripheral effects. These findings may explain some of the clinical reports of urinary incontinence with risperidone and may predict similar occurrences with olanzapine therapy.

Effects of the atypical neuroleptic clozapine on micturition parameters in anesthetized rats.

Clozapine, an atypical antipsychotic, has resulted in a number of reports of urinary disturbances in the clinical literature. We examined the effects of clozapine on urodynamic parameters in the anesthetized rat and compared the effects to those of the typical antipsychotic haloperidol and the selective D2 and D4 antagonists, raclopride and L-745,870, respectively. Clozapine abolished high-frequency oscillations (HFO) during the expulsion phase, and profoundly altered a number of other parameters (e.g., intercontraction interval and resting pressure). Clozapine did not affect the peak contraction pressure during cystometrograms but displayed peripheral inhibition of bladder contractions elicited by electrical stimulation of the pelvic nerve (possibly mediated via clozapine's anti-muscarinic effects). Haloperidol had less potent effects than clozapine since it reduced the amplitude of HFO to 25% of control and also affected several other parameters but without peripheral bladder inhibition. Raclopride only resulted in a modest decrease (approximately 70% of control) in the HFO and no alteration in other parameters. L-745,870 was effective only at highest dose tested suggesting that it might not be acting selectively at D4 receptors. Therefore, we propose that clozapine primarily interferes with the function of the external urethral sphincter. These effects can only be partly explained through antagonism of D2 receptors. Since both clozapine and haloperidol have interactions with other transmitter systems beside dopamine, we suggest that central antagonism of D2 receptors, coupled to central antagonism of another receptor system and peripheral muscarinic receptor blockade, may account for clozapine's potent effects on micturition.

Clozapine inhibits micturition parameters and the external urethral sphincter during cystometry in anesthetized rats.

Clozapine therapy has been associated with a high degree of urinary disturbances. The purpose of this study is to examine the effect of clozapine on urodynamic parameters and on the activity of the external urethral sphincter in anesthetized rats. Single cystometrograms (CMG) were performed on urethane-anesthetized female Sprague-Dawley rats, while also recording the EMG from the external urethral sphincter. Clozapine (0, 0.1, 1, 10 mg/kg) was administered intravenously. In addition, the peripheral end of the pudendal nerve was stimulated in order to determine if clozapine was exerting peripheral effects directly on the external urethral sphincter. Clozapine increased the bladder capacity while reducing the micturition volume thus resulting in a marked increase in the residual volume. The pressure threshold was increased but the peak pressure during contraction remained unchanged. The expulsion time and contraction time were decreased and the amplitude of the high frequency oscillations (HFO) seen during the expulsion phase were markedly reduced and even abolished. The EMG from the external urethral sphincter also showed marked decreases after clozapine, and the bursting pattern seen during HFO was abolished. Clozapine had no effect on the activity elicited from electrical stimulation of the pudendal nerve. Clozapine inhibits several urodynamic parameters and inhibits the activity of the external urethral sphincter in anesthetized rats. These effects may help explain the urinary disturbances reported in the clinical literature.

Separate urinary bladder and external urethral sphincter neurons in the central nervous system of the rat: simultaneous labeling with two immunohistochemically distinguishable pseudorabies viruses.

This work examines the distribution, in the central nervous system, of virus-labeled neurons from the rat urinary bladder and the external urethral sphincter simultaneously within the same tissue sections. Two immunohistochemically distinct pseudorabies virus strains were injected into male Sprague--Dawley rats (approximately 280 g). One virus was injected into the bladder and the other into the external urethral sphincter. After incubation intervals of 2, 2.5 and 3 days, sections from the spinal cord and brain were treated immunohistochemically to detect cells which were labeled separately by each virus or were labeled by both viruses. The major result of these experiments is that each strain of virus labeled a separate population of neurons and that some neurons were labeled by both strains. In the lumbosacral cord, 3 days post-infection, neurons labeled by virus from the external urethral sphincter were found in Onuf's nucleus, the dorsal gray commissure, and the superficial dorsal horn. Neurons labeled by virus from the urinary bladder were found in the L6--S1 and L1--L2 spinal cord segments within the dorsal gray commissure, the intermediolateral area and the superficial dorsal horn. Double-labeled interneurons were mainly located in the dorsal gray commissure although some were also found in the intermediolateral area and the superficial dorsal horn. In the medulla, external urethral sphincter neurons and bladder neurons and double-labeled neurons were found in the reticular region and the raphe. More rostrally, bladder neurons were located in the pontine micturition center and external urethral sphincter neurons were found in the locus coeruleus and subcoeruleus. A very small number of double-labeled neurons were found in the pontine micturition center and the locus coeruleus or subcoeruleus.

Anatomical evidence for two spinal 'afferent-interneuron-efferent' reflex pathways involved in micturition in the rat: a 'pelvic nerve' reflex pathway and a 'sacrolumbar intersegmental' reflex pathway.

We labeled interneurons in the L1-L2 and L6-S1 spinal cord segments of the rat that are involved in bladder innervation using transneuronal retrograde transport of pseudorabies virus (PRV) in normal animals and in animals with selected nerve transections. Preganglionic neurons were identified using antisera against choline acetyltransferase (ChAT). In some experiments we labelled parasympathetic preganglionic neurons (PPNs) in the L6-S1 spinal cord by retrograde transport of Fluorogold from the major pelvic ganglion. We identified bladder afferent terminals using the transganglionic transport of the anterograde tracer cholera toxin subunit b. We present anatomical evidence for two spinal pathways involved in innervation of the bladder. First, in the intact rat, afferent information from the bladder connects, via interneurons in L6-S1, to the PPNs that provide the efferent innervation of the bladder. The afferent terminals were located mainly in close apposition to interneurons located dorsal to the retrogradely labeled PPNs. Second, using L6-S1 ganglionectomies or L6-S1 ventral root rhizotomies we limited viral transport to the sympathetic pathways innervating the bladder. This procedure also labelled interneurons (but not PPNs) with PRV in the L6-S1 spinal cord in a location very similar to those described in the intact rat. These interneurons also receive bladder afferent terminals but we propose that they project to sympathetic preganglionic neurons, most of which are in the L1-L2 spinal segments. Based on this anatomical evidence, we propose the existence of two spinal reflex pathways involved in micturition: a pathway limited to a reflex arc in the pelvic nerve (presumably excitatory to the detrusor muscle); and a pathway involving the pelvic nerve and sympathetic nerve fibers, some of which may travel in the hypogastric (presumably inhibitory to the detrusor muscle).

The predictive value of intraoperative somatosensory evoked potential monitoring: review of 244 procedures.

INTRODUCTION: There is some controversy regarding the value of intraoperative neurophysiological monitoring in predicting postoperative neurological deficits. We discuss our experience with the use of intraoperative somatosensory evoked potentials (SSEPs) during surgery of cranial base tumors. METHODS: We retrospectively reviewed all of the procedures that had been performed for the resection of cranial base tumors from July 29, 1993, through March 16, 1995. One hundred ninety-three consecutive patients had undergone a total of 244 procedures. SSEP waveforms were classified as follows: Type I, no change; Type II, change that reverts to baseline; Type III, change that does not revert to baseline; and Type IV, complete flattening of the SSEP waveform without improvement. Two patients had no waveforms from the beginning of the case (Type V) and were excluded from further analysis. New immediate postoperative neurological deficits were recorded. RESULTS: There were 64 male and 129 female patients, with a mean age of 46.6 years. One hundred seventy-seven patients had Type I SSEP waveforms, 13 of whom had postoperative deficits (7%). Fifty-six patients had Type II SSEPs, and nine (16%) of them had postoperative neurological deficits. Six patients had Type III SSEPs, and three had Type IV SSEPs, all of whom (100%) had postoperative deficits. There was a correlation between SSEP type and the results of the postoperative neurological examinations. The positive predictive value is 100%, and the negative predictive value is 90%. Although a change in the waveform that did not revert to baseline (Types III and IV) always predicted a postoperative deficit, a normal waveform did not always rule out postoperative deficits. Pathological abnormality, vessel encasement, vessel narrowing, degree of cavernous sinus involvement, brain stem edema, middle fossa location, final amount of resection, age, and tumor size correlated with a high predictive value of SSEP monitoring on univariate analysis (P < 0.05). None of these variables correlated significantly on multivariate analysis (P > 0.05), although brain stem edema was close (P = 0.0571). CONCLUSION: Intraoperative SSEPs have a high positive predictive value during surgery for cranial base tumors, but they do not detect all postoperative deficits.

Origins of the sympathetic innervation of the cervical end of the uterus in the rat.

A retrograde neuronal tracer (Fast Blue) was injected in the cervical end of the uterine horn of virgin rats. The majority of the retrogradely labeled post-ganglionic sympathetic neurons were found in the sympathetic chain (74%). The superior mesenteric ganglia, inferior mesenteric ganglia and suprarenal ganglia accounted for 22, 3 and < 1%, respectively. The distribution of neurons in the sympathetic chain labeled from the uterus resembles that described for other pelvic organs.

Neurons in the rat brain and spinal cord labeled after pseudorabies virus injected into the external urethral sphincter.

Male Sprague-Dawley rats, with their pelvic and hypogastric nerves transected, were infected with pseudorabies virus (PRV) injected into the external urethral sphincter. Animals were sacrificed at 2, 2.5, 3, and 4 days postinfection. Spinal cord and brain tissue were sectioned and processed by immunohistochemical techniques with antisera against PRV and choline acetyl transferase (CAT). At 2 days postinfection, virus-labeled neurons were found in the ventrolateral divisions of Onuf's nucleus and in the dorsal gray commissure (DGC). At progressively later incubation times, labeled neurons were found in the intermediolateral regions, the superficial layer of the dorsal horn, and the brainstem, in particular, the pontine micturition center. PRV/CAT-positive neurons were only found in Onuf's nucleus. Preganglionic neurons in the L6-S1 intermediolateral regions were CAT positive but PRV negative, thus suggesting that they are interneurons, not sacral parasympathetic preganglionic neurons. After 4 days, virus had spread to neurons in the paraventricular, preoptic, and even cortical regions. The distribution of these PRV-labeled brain neurons strongly resembled that obtained after the injection of PRV into the urinary bladder (Nadelhaft et al. [1992] Neurosci. Lett. 143:271-274). In both cases, neurons were labeled in the DGC in the spinal cord. The data therefore suggest that neurons in the DGC may be involved in the integrated control of the bladder and the external urethral sphincter.

Central nervous system neurons infected by pseudorabies virus injected into the rat urinary bladder following unilateral transection of the pelvic nerve.

Following the transection of one pelvic nerve and both hypogastric nerves, the urinary bladder of male Sprague-Dawley rats was injected with pseudorabies virus (PRV; Bartha strain). The central stump of the transected pelvic nerve was labelled with fast blue (FB), and rats were maintained for 2, 2.5, and 3 days following viral infection. Tissue was processed with antisera against PRV and choline acetyltransferase (CAT). In the L6-S1 spinal cord, neurons in the ipsilateral intermediolateral area (IML) were labelled after 2 days. After 2.5 days, labelled neurons were also found in the dorsal gray commissure (DGC), the ipsilateral superficial dorsal horn, and the contralateral IML area. After 3 days, many labelled neurons appeared in the superficial dorsal horns and, bilaterally, in the L6-S1 dorsal root ganglia. In both IMLs, two groups of PRV-labelled neurons were found: 1) CAT-positive preganglionic cells and 2) smaller, CAT-negative cells located slightly dorsal to the preganglionic neurons. No other doubly stained neurons were found in the spinal cord. Contralateral DRG neurons stained for either PRV or FB or both. Ipsilateral DRG neurons stained only for PRV. PRV-immunoreactive (IR) neurons appeared in the brainstem only after 3 days. These were located primarily in the pontine micturition centers (equal numbers), the ventral locus coeruleus, and the raphe and lateral reticular areas.

Neurophysiologic monitoring during cranial base surgery: is it necessary?

Intra-operative neurophysiologic monitoring is here to stay. Future improvements of technique will allow neurophysiologists to monitor many brain and CN functions not reliably monitored at present. It is expected that such monitoring will become a routine part of all complex neurosurgical operations, despite the current pressure to reduce the cost of health care.

Hypertrophic neurons innervating the urinary bladder and colon of the streptozotocin-diabetic rat.

Female rats were made diabetic with an intravenous injection of streptozotocin (STZ) producing bladder hypertrophy. Using fluorescent dyes injected into the bladder or the colon, we have measured the size of neurons in various ganglia associated with these organs in control and STZ-diabetic rats. These include (1) postganglionic neurons in the pelvic ganglion, (2) postganglionic neurons in the inferior mesenteric ganglion, (3) dorsal root ganglion neurons, (4) sympathetic chain ganglion neurons, (5) preganglionic neurons in the sacral parasympathetic nucleus, (6) motor neurons in Onuf's nucleus innervating the external urethral sphincter. In addition we have measured neurons in some of these groups for rats which have been maintained on a 5% sucrose in water and restricted food diet. In the STZ-diabetic animals only those neurons which make direct contact with the bladder or the colon were found to be hypertrophied (15-70%). In the diuretic animals, only neurons directly innervating the bladder exhibited hypertrophy. We speculate that a trophic factor transported from the organ to the neuron is responsible for this effect.

Afferent and sympathetic innervation of the dome and the base of the urinary bladder of the female rat.

The afferent and sympathetic innervation of different regions of the urinary bladder (bladder dome vs. bladder base) was examined in the female rat using simultaneous injections of two fluorescent tracers. Retrogradely labeled cells were found in the dorsal root ganglia (DRG; L1-L3 and L6-S1), the sympathetic chain (SC; T12-L6), the inferior mesenteric ganglia (IMG) and the major pelvic ganglia (MPG). There were very few double-labeled cells, indicating that the dome and the base of the bladder receive innervation (afferent or sympathetic) from separate and distinct neuronal populations. Most of the sympathetic innervation of the bladder arose from the SC (dome: 77%; base: 89%) and it was carried equally by the hypogastric and pelvic nerves. The distributions of SC postganglionic neurons innervating the dome and the base of the bladder were very similar. In contrast, the contribution of IMG neurons was almost entirely restricted to the dome of the bladder (22%), with less than 1% innervating the base. Tyrosine hydroxylase-immunoreactive (TH) neurons in the MPG displayed a strong sexual dimorphism. Many TH neurons were found in the male MPG, but very few in the female MPG. In the female, these TH neurons projected almost exclusively to the bladder base of the female rat and were responsible for 10% of the sympathetic innervation of the base. Less than 1% innervated the dome. Therefore, prevertebral ganglia (IMG and MPG) show a strong regional selectivity in the innervation of the bladder of the female rat. The possible functional implications of this organization are discussed.

Multiple putative neuromessenger inputs to the phrenic nucleus in rat.

Immunohistochemical reactions for 12 putative neuromessengers combined with retrograde labeling of phrenic motoneurons identified seven neuromessengers (5-hydroxytryptamine, substance P, thyrotropin-releasing hormone, methionine enkephalin, cholecystokinin, galanin, neuropeptide Y) located within terminal varicosities in the phrenic nucleus. The degree of terminal labeling in the phrenic nucleus varied depending on the peptide. Substance P, thyrotropin-releasing hormone and methionine enkephalin were each tested for colocalization with 5-hydroxytryptamine within terminal varicosities in the phrenic nucleus, and the coincidence of double-labeling varied for each peptide. These results indicate that phrenic motoneurons are subject to modulation by many peptide neuromessengers that may alter their responsiveness to primary excitatory and inhibitory inputs.

Central nervous system neurons labelled following the injection of pseudorabies virus into the rat urinary bladder.

Pseudorabies virus was injected into the wall of the urinary bladder and, following incubation times of 2, 3 and 4 days, central nervous tissue was processed immunohistochemically for the presence of virus. Longer incubation times resulted in more extensive spread of the virus. Infected neurons were initially found in the spinal cord (mainly lumbosacral) and, after longer survival times, in raphe nuclei, reticular area, pontine micturition center, locus coeruleus, red nucleus, hypothalamus, preoptic, and cortical areas. These data define a multisynaptic circuit of neurons whose ultimate output influences urinary bladder function.

Reduced urinary bladder afferent conduction velocities in streptozocin diabetic rats.

Previous experiments in our laboratory have described the method used to measure the conduction velocity distribution of a selected group of fibers (Brain Res., 520 (1990) 83-89). We have applied this technique to the 2 month streptozotocin-diabetic rat. Glycosylated hemoglobin values measured at the time of death were 17.19 +/- 4.74% (diabetic, n = 8) and 4.07 +/- 0.74% (controls, n = 6). Diabetic bladders were thicker and heavier. The wet weights were 0.50 +/- 0.11 g (diabetic, n = 7) and 0.16 +/- 0.01 g (controls, n = 6). The conduction velocities of a total of 151 and 86 single afferent fibers were measured in the diabetic and control animals respectively. The conduction velocity distribution of the diabetics showed a shift towards slower speeds when compared to controls. The mean conduction velocities were 1.70 m/s for diabetics and 2.84 m/s for controls. The percent of units with conduction velocities greater than 2.5 m/s was 17.2 for diabetics and 36.0 for controls. This experiment demonstrates, for the first time, that diabetes causes a significant reduction of afferent conduction velocities in a functionally well-defined system.

MK-801, a non-competitive NMDA receptor antagonist, produces facilitation of the micturition reflex in awake, freely-moving rats.

MK-801 (dizocilpine), a non-competitive N-methyl-D-aspartate (NMDA) receptor blocker, produced a dose-dependent (30-120 micrograms/kg, i.v.) increase in the frequency of micturition (as well as the already described behavioral effects) in awake, freely-moving rats. The contraction amplitude was also slightly increased. In contrast, MK-801 administered to urethane-anesthetized rats resulted in complete inhibition of bladder contractions. The effect of MK-801 on the frequency of bladder contractions, therefore, is anesthetic dependent. Excitatory amino acids acting at NMDA receptors may play a role in the control of micturition.