José Luis González-Mora

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.

Preparation of core–shell Fe3O4@poly(dopamine) magnetic nanoparticles for biosensor construction

Novel core-shell Fe3O4@poly(dopamine) magnetic nanoparticles were prepared through an in situ self-polymerization method. The hybrid nanomaterial showed an average core diameter of 11 ± 3 nm and a polymer thin film thickness of 1.8 ± 0.2 nm. The core-shell nanoparticles were employed as solid supports for the covalent immobilization of horseradish peroxidase (HRP), and the resulting biofunctionalized magnetic nanoparticles were employed to construct an amperometric biosensor for H2O2. The enzyme biosensor showed a high sensitivity of 442.14 mA M-1 cm-2, a low limit of detection of 182 nM, a wide linear range from 6.0 × 10-7 to 8.0 × 10-4 M and high stability for 1 month.

Amphetamine increases the extracellular concentration of glutamate in striatum of the awake rat : involvement of high affinity transporter mechanisms

Using microdialysis it was found that intracerebral infusions of amphetamine increase the extracellular concentration of glutamate, and also of dopamine, aspartate, GABA, and taurine. The increases in glutamate produced by amphetamine was independent of calcium in the perfusion medium but was significantly attenuated by specific blockers of the high affinity transporters of this neurotransmitter. Amphetamine infusions also produced a decrease in the extracellular concentration of Na+, an increase in the extracellular concentration of lactate, and a decrease in haemoglobin in the area of perfusion. All these data suggest that amphetamine increases the extracellular concentration of glutamate and other neurotransmitters through a hypoxic mediated process. This study also shows that an alpha-noradrenergic receptor antagonist is able to attenuate the effects of amphetamine on the release of glutamate, dopamine, GABA and taurine, which further suggests a vasoconstrictor effect of amphetamine as a result of which hypoxia could develop.

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.

Changes in Mating Behavior, Erectile Function, and Nitric Oxide Levels in Penile Corpora Cavernosa in Streptozotocin-Diabetic Rats

Abstract This study assessed whether the in vivo production of nitric oxide (NO) in the penis is impaired in experimental diabetes and whether this phenomenon can be explained by abnormal levels of NO synthase isoenzymes and/or plasma androgens. Adult male Sprague-Dawley rats were injected with streptozotocin (STZ) (40 mg/kg, i.p.) or vehicle. One half of the STZ-treated animals received daily insulin replacement. Twelve weeks later, the animals were tested for mating behavior and erectile reflexes. They were then anesthetized with urethane (1 g/kg), and the NO levels in their corpora cavernosa were monitored electrochemically with porphyrin microsensors before and after electrostimulation of the cavernous nerve. The intracavernous pressure (ICP) was measured simultaneously. The diabetic animals had substantial impairment in the mating and erectile reflexes tests, decreased basal and stimulated NO levels in the corpora, and a reduced ICP response to cavernous nerve stimulation. Insulin replacement fully reversed the effects of diabetes on the mating reflexes, the basal NO signals, and the ICP responses to electrical field stimulation and partially restored the stimulated NO release. Neither diabetes nor diabetes with insulin treatment had significant effects on serum testosterone levels or NOS isoform (nNOS, eNOS, and iNOS) protein content in penile homogenates, indicating that the changes found in erectile function were independent of such variables. These results also suggest that the diabetes-induced reduction in corporeal NO levels could be mainly due to the lack of some essential cofactors for NOS activity rather than to changes in the amount of enzyme proteins.

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.

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.

Fixed Versus Removable Microdialysis Probes for In Vivo Neurochemical Analysis: Implications for Behavioral Studies

Abstract: 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.

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.

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.