Biomedical subjects

J L Gonzalez-Mora

Publications and source records attributed to J L Gonzalez-Mora.

14 recordsLinked to original sources

PubMed1999

Nitric oxide release in penile corpora cavernosa in a rat model of erection.

1. Nitric oxide (NO) levels were measured in the corpus cavernosum of urethane-anaesthetized rats by using differential normal pulse voltammetry with carbon fibre microelectrodes coated with a polymeric porphyrin and a cation exchanger (Nafion). A NO oxidation peak could be recorded at 650 mV vs. a Ag-AgCl reference electrode every 100 s. 2. This NO signal was greatly decreased by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), given by local and systemic routes, and enhanced by the NO precursor L-arginine. Treatment with L-arginine reversed the effect of L-NAME on the NO peak. 3. Both the NO signal and the intracavernosal pressure (ICP) were increased by electrical stimulation of cavernosal nerves (ESCN). However, the rise in the NO levels long outlived the rapid return to baseline of the ICP values at the end of nerve stimulation. 4. The ICP and the NO responses to ESCN were suppressed by local and systemic injections of L-NAME. Subsequent treatment with L-arginine of L-NAME-treated animals restored the NO signal to basal levels and the NO response to ESCN. The ICP response to ESCN was restored only in part by L-arginine. 5. The observed temporal dissociation between the NO and ICP responses could be accounted for by several factors, including the buffering of NO by the blood filling the cavernosal spaces during erection. 6. These findings indicate that an increased production of NO in the corpora cavernosa is necessary but not sufficient for maintaining penile erection and suggest a complex modulation of the NO-cGMP-cavernosal smooth muscle relaxation cascade.

Anesthesia↗

PubMed1997

Constitutive NOS isoforms account for gastric mucosal NO overproduction in uremic rats.

To study whether renal failure enhances gastric mucosal nitric oxide (NO) formation in the rat, we measured 1) in vivo NO concentration and 2) NO synthase (NOS) activity, content, and mRNA expression in gastric mucosal homogenates of uremic and sham-operated anesthetized rats. Gastric mucosal NO release was measured by an electrochemical technique. NOS content was analyzed by Western immunoblots, using specific monoclonal antibodies. Constitutive (Ca2+ dependent; cNOS) and inducible (Ca2+ independent; iNOS) NOS activities were assayed by following the conversion of L-[U-14C]arginine to [U-14C]citrulline. mRNA expression for the constitutive neuronal (ncNOS), endothelial (ecNOS), and iNOS isoforms was determined by reverse transcription-polymerase chain reaction. Under basal conditions, gastric mucosal NO concentration was significantly greater in uremic compared with control rats. This was accompanied by significantly greater gastric mucosal cNOS activity in uremic rats than in control rats, whereas no differences were observed in iNOS activity between both groups of animals. Moreover, total enzyme content and the levels of gastric mucosal mRNA expression for ncNOS, ecNOS, and iNOS showed no significant differences between uremic and sham-operated rats. These data confirm that, in uremic rats, enhanced Ca2+-dependent NOS activity is responsible for gastric mucosal NO overproduction and suggest that the main regulatory mechanism is not transcriptional but translational and/or posttranslational in nature.

Animals↗

PubMed1996

In vivo monitoring of brain neurotransmitter release for the assessment of neuroendocrine interactions.

1. The neurotransmitter mechanisms regulating neuroendocrine processes have been traditionally inferred from the effects of drugs purportedly acting through specific transmitter systems. The direct appraisal of changes in endogenous neuromediators had to rely initially on analyses of brain samples obtained post-morten. 2. Currently, a more physiological assessment is available through the monitoring ot the extracellular levels of neurotransmitters and their metabolites in discrete brain areas of living animals. Two methodologies, namely in vivo voltammetry and microdialysis, are being increasingly used for this purpose. This article summarizes their principles, relative merits, and limitations and presents some relevant applications. 3. Thus, microdialysis data show a differential response in the amphetamine-induced dopamine release in the nucleus accumbens in adult male and female rats castrated prepuberally. Given their high time-resolution, in vivo electrochemistry techniques seem especially suited for studying the fast, non-genomic effects of steroid hormones. This is illustrated by the voltammetric detection of a rapid release of dopamine in the corpus striatum induced by progesterone in males. 4. These methodologies should be regarded as complementary tools for the assessment of the neurochemical correlates of neuroendocrine interactions.

Animals↗

PubMed1995

Neurochemical correlates of sexual exhaustion and recovery as assessed by in vivo microdialysis.

The extracellular levels of the dopamine (DA) metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the medial preoptic area (MPOA) of male rats were monitored during unrestricted copulation, the ensuing state of sexual refractoriness and the resumption of mating activity. MPOA dialysates were collected from the same animal during four consecutive days. In the first day the subjects were allowed to copulate until reaching a satiation criterion. That was associated with a marked increase in the dialysate levels of the three metabolites assessed. During the next two days the animals remained sexually inactive when exposed to receptive females. Their basal levels of DOPAC and HVA were elevated, whereas those of 5-HIAA remained as low as in the first session. During the non-mating exposure to receptive females there were only minor changes in the three metabolites. By the fourth day, just before the animals resumed copulation, the basal levels of the DA metabolites, especially HVA, had decreased to values closer to those found in the first day. When they mated again to exhaustion the levels of DOPAC, HVA, and 5-HIAA increased as in the first session. The neurochemical changes found during the intervening state of sexual inactivity (i.e. increased levels of DA metabolites) are reminiscent of the effects of DA receptor blockers, which suggests a possible neurochemical mechanism for sexual refractoriness.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Changes in monoamine turnover in forebrain areas associated with masculine sexual behavior: a microdialysis study.

This report compares the changes in the main dopamine (DA) and serotonin (5-HT) metabolites, respectively dihydroxyphenylacetic acid (DOPAC) and 5-hydroxy indoleacetic acid (5-HIAA) in three relatively close brain regions, namely the nucleus accumbens (ACB), the medial preoptic area, and the medial basal hypothalamus (MBH), as well as DA in the ACB, of copulating male rats. All these neurochemicals remained fairly stable when the animals were exposed to non sexual social stimuli (castrated females), and they increased during mating with receptive females. There were regional differences in these copulation-related changes, however, with those in the MBH being shorter-lived. There were also differences in the time-course of the changes in DOPAC and 5-HIAA the latter being slower. It is suggested that they reflect the involvement of the DA and 5-HT innervation of diencephalic structures in, respectively the appetitive and consummatory/satiation mechanisms of sexual behavior. The physiological relevance of these neurochemical changes is supported by the lack of differences between the standard measures for sexual behavior recorded before surgery and during the dialysis session.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Fixed versus removable microdialysis probes for in vivo neurochemical analysis: implications for behavioral studies.

The levels of several neurochemicals, i.e., uric acid (UA), dopamine (DA), dihydroxyphenylacetic acid, and 5-hydroxyindoleacetic acid, collected daily from the rat striatum with either fixed or removable microdialysis probes for 7 days after surgery were compared. The implantation of the fixed cannula was followed by a 10-fold increase in the UA content in the dialysates collected from the first day after surgery onward and by a steady decrease in dihydroxyphenylacetic acid levels, whereas those of DA remained fairly stable. With the removable cannula system, only a smaller, transient increase in UA during the first 3 days after surgery was observed, with no change in DA or monoamine metabolites. The glial reaction around the cannula tracks was assessed by both quantitative histological techniques and measuring the glutamine levels in the dialysates collected at the time of surgery and 7 days later. Both the glial cell number and nuclear size, as well as the glutamine outflow, were considerably larger in the animals implanted with the fixed probes. It is, therefore, likely that the UA levels in the dialysate reflect the glial reaction to the probe. The suitability of the removable probe system for behavioral experiments involving repeated microdialysis sampling was illustrated in an experiment showing that the DA release in the nucleus accumbens of male rats assessed daily at postsurgery days 5-10 was virtually identical in three alternating sessions of sexual behavior as was the smaller release of this neurotransmitter detected during intervening nonsexual social interactions.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Voltammetric monitoring of brain extracellular levels of serotonin, 5-hydroxyindoleacetic acid and uric acid as assessed by simultaneous microdialysis.

We have previously developed a microcomputer-assisted curve-fitting method for measuring the components of the mixed electrochemical signals recorded by differential normal pulse voltammetry in the living brain. It was initially used for resolution of the dopamine and dihydroxyphenylacetic acid components of the catechol signal (peak 2). This report shows how it can be applied to analysis of the indoleamine/uric acid (UA) components of the more complex peak 3. The voltammogram is modeled as a mixture of 3 normal curves of known parameters corresponding to the oxidation of UA, 5-hydroxyindoleacetic acid and serotonin, which is solved by non-linear iterative procedures. Performance was assessed by treatments with drugs having well-known effects on the substances monitored, pargyline and allopurinol, and by the chromatographic analysis of microdialysates collected simultaneously from the contralateral side.

Allopurinol↗

PubMed1991

Sex-related olfactory stimuli induce a selective increase in dopamine release in the nucleus accumbens of male rats. A voltammetric study.

Changes in the dopaminergic (DA) transmission in the nucleus accumbens were investigated in male rats exposed to sociosexual olfactory stimuli from different conspecifics: receptive female, non-receptive female and intact male. DAergic transmission was assessed by measurement of extracellular levels of DA and dihydroxyphenylacetic acid (DOPAC). Both compounds were recorded by using differential normal pulse voltammetry (DNPV) with electrochemically pretreated carbon fiber electrodes and numerical analysis of the catechol peak. Exposition to receptive female odors induced a marked and selective increase in DA release compared to control values. Exposition to non-receptive female odors and male odors induced an increase in DA release not significantly different from that following the change of environment. In conclusion, mesencephalic DAergic neurons reaching the nucleus accumbens appear to be involved in the perception of behaviorally significant olfactory cues.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Mathematical resolution of mixed in vivo voltammetry signals. Models, equipment, assessment by simultaneous microdialysis sampling.

A microcomputer-assisted curve-fitting procedure was developed for the quantitative estimation of the components of the mixed "catechol peak" recorded with differential normal pulse voltammetry (DNPV) at electrochemically pretreated carbon fiber microelectrodes in the living brain. The contribution of each of the relevant electroactive species is fitted by a normal probability function, the parameters of which are previously determined in vitro for each electrode and substance. The voltammogram is thus modeled as a mixture of normal curves corresponding to the individual oxidizable substances plus a low order polynomial approximating the baseline. In a former approach the function was solved by linear least squares techniques. As a further improvement, we now propose a non-linear model of the voltammogram and a Gauss-Newton iterative algorithm with stepwise regression for parameter estimation. This report shows the application of the method for the resolution of the dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) components of the DNPV signal recorded from the striatum of freely moving animals in response to amphetamine and pargyline. The method was validated by the chemical assay of contralateral microdialysates collected simultaneously. The changes detected by both methodologies were closely parallel, with highly significant correlation coefficients (0.87 and 0.99 for DA and DOPAC, respectively, P less than 0.001). This study further illustrates that the in vivo voltammetry methodology can be improved substantially by incorporating a suitable mathematical treatment of the electrochemical signals.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Anomalously high concentrations of brain extracellular uric acid detected with chronically implanted probes: implications for in vivo sampling techniques.

The height of peak 2, h2, recorded using linear sweep voltammetry with 350-micron-diameter carbon paste electrodes in rat striatum was measured from the day of implantation (day 0) to 4 months after surgery. The value of h2 was at a minimum on day 0 (0.6 +/- 0.2 nA; n = 20), rose sharply to a maximum on day 2 (6.3 +/- 0.9 nA; n = 12), and decreased to a stable level by day 7 (3.3 +/- 0.7 nA; n = 16), which lasted for 4 months (3.2 +/- 0.6 nA; n = 9). These changes were shown by microinfusion of uricase to be due to variations in the concentrations of extracellular uric acid, although h2 appears to have a small baseline contribution of approximately 0.3 nA from 5-hydroxyindoleacetic acid. The stable value of h2 recorded under chronic conditions was estimated to correspond to a minimal uric acid concentration of 50 mumol/L, which represents a 10-fold increase in the extracellular level of this purine metabolite compared with the initial (acute) value. Very similar results were obtained using a microdialysis technique that detected uric acid directly. These estimates of striatal uric acid concentration are in marked contrast to those obtained using 40-micron diameter carbon fiber electrodes, which showed a decrease from the acute preparation to less than 1 mumol/L under chronic conditions. Large values of h2 were also recorded with chronically implanted paste electrodes in the hippocampus and frontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Increased dopamine release in the nucleus accumbens of copulating male rats as evidenced by in vivo voltammetry.

This report describes the changes in extracellular levels of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) detected in the nucleus accumbens of male rats engaged in copulatory activity. They were monitored by using differential normal pulse voltammetry (DNPV) with electrochemically pretreated carbon fiber microelectrodes and numerical analysis of the catechol signal. The copulatory pattern displayed during the voltammetric recordings was similar to those recorded prior to surgery. Copulating animals showed a conspicuous increase in the DA and DOPAC electrochemical signals up to, respectively, 170% and 150% of baseline levels. This response was much attenuated when the experimental animals were exposed to either non-receptive castrated females or intact males. These data are consistent with the permissive role currently ascribed to the dopaminergic innervation of the n. accumbens in the selection and the initiation of behavioral adaptive sequences.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

In vivo voltammetry study of the modulatory action of prolactin on the mesolimbic dopaminergic system.

The effects of an acute subcutaneous injection of ovine prolactin (PRL) or its vehicle on total motor activity and the extracellular levels of dopamine (DA), DOPAC and ascorbic acid (AA) in the nucleus accumbens were monitored simultaneously in freely behaving male rats. The neurochemical data were obtained by Differential Normal Pulse Voltammetry using electrochemically pretreated carbon fiber microelectrodes and numerical waveform analysis of the catechol peak. PRL treatment increased the extracellular levels of DA and DOPAC in the nucleus accumbens, which is consistent with previous reports using other methodologies. Furthermore, there was a concomitant decrease in the AA signals and motor activity. These findings suggest an antagonistic action of PRL on dopaminergic transmission in the mesolimbic system.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1988

Concurrent on-line analysis of striatal ascorbate, dopamine and dihydroxyphenylacetic acid concentrations by in vivo voltammetry.

A new method for on-line analysis of in vivo differential normal pulse voltammograms is reported. They are fitted by least squares to an expression describing the contribution of different electroactive species and the baseline. Its validity for resolving ascorbate (AA), dopamine (DA) and DOPAC signals is evidenced by both in vitro testing and the changes recorded in the striatum of anesthetized rats following drug treatments having well-known effects on DA release and metabolism. Thus, pargyline and amphetamine treatments respectively increased and decreased DA and DOPAC, whereas they both were increased by haloperidol. AA levels followed those of DA except when haloperidol was given.

3,4-Dihydroxyphenylacetic Acid↗

PubMedDate not supplied

Post-mortem dopamine dynamics assessed by voltammetry and microdialysis.

The effects of total brain ischemia (decapitation) on striatal extracellular levels of dopamine (DA) dihydroxyphenyl acetic acid (DOPAC) and ascorbic acid (AA) in chloral hydrate anesthetized rats were monitored at 1-min intervals by differential normal pulse voltammetry (DNPV) with numerical deconvolution of the catechol peak. Changes in pH were assessed by the shift of AA oxidation potential and incorporated into the computational procedure. The AA peak showed a sharp, short-lived (less than 15 min) postdecapitation rise, followed by a slower secondary increase. The DA signal increased 100-fold in the first 20 min followed by a slow decline. DOPAC levels fell 80% within 15 min after death. The post-mortem changes in extracellular DA and DOPAC were verified by a similar experiment using microdialysis. These observations probably reflect massive release and impaired uptake of DA combined with reduced monoamine oxidase activity. Changes in membrane permeability to DOPAC as a consequence of a post-mortem drop in pH may also contribute to the decline in extracellular DOPAC levels.

3,4-Dihydroxyphenylacetic Acid↗