Manuel Mas

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.

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.

Voltammetric and microdialysis monitoring of brain monoamine neurotransmitter release during sociosexual interactions

The monoamine neurotransmitters have long been ascribed important modulatory actions on male sexual behavior by a wealth of pharmacological studies. Methodological developments have now made possible the assessment of the extracellular levels of amine transmitters and their metabolites in discrete brain areas of sexually behaving animals using in vivo voltammetry and microdialysis. Studies in our and other laboratories consistently show increased dopamine release in forebrain structures known to be involved in mating activity, including the nucleus accumbens and the medial preoptic area, during both the appetitive (i.e., non-contact exposure to sexual stimuli) and consummatory phases of this behavior. Serotonin utilization seems to be mainly related to consummatory events. These findings are consistent with the pharmacological evidence as well as previous ex vivo work. The state of sexual inactivity that follows unrestricted mating associates with increased dopamine turnover in the preoptic area. According to the available information, it could reflect some blockade of dopaminergic receptors, possibly involving prolactin. No disturbance of ongoing sexual behavior was observed during the neurochemical monitoring sessions with either methodology. These studies show voltammetry and microdialysis as powerful complementary tools for the assessment of sociosexual interactions.

Neurochemical correlates of male sexual behavior

This report presents evidence of changes in the concentration of monoamine neurotransmitters and their metabolites in homogenates of spinal cord and brain areas of male rats related to specific events of their mating behavior. Intact male rats were allowed to copulate with receptive females and decapitated immediately after either the first intromission or the first ejaculation. Non-mating control animals were exposed to other males, instead of females. The concentration of monoamines (norepinephrine, dopamine and serotonin) and some of their major metabolites (DOPAC and HIAA) in homogenates of discrete brain areas (parietal cortex, preoptic region, mediobasal hypothalamus) and lumbosacral spinal cord were measured by HPLC-ED. Results suggest that sexual arousal is associated with both increased dopaminergic activity in the preoptic region and inhibition of descending monoaminergic signals to the lumbosacral cord, whereas ejaculation is accompanied by increased activity of the serotonergic, as well as dopaminergic, innervation of the preoptic region. These findings give neurochemical support to notions of central monoamines involvement in sexual behavior suggested by previous pharmacological studies.

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.

Androgens stimulate preoptic area Na+,K+-ATPase activity in male rats

This paper describes the effects of castration and testosterone replacement on the Na+,K+-ATPase activity levels of the cerebral cortex (CC), preoptic-suprachiasmatic region (POSC) and mediobasal hypothalamus (MBH) in male rats. Na+,K+-ATPase activity was estimated as the ouabain-sensitive fraction of ADP and AMP generation rate, measured by high-pressure liquid chromatography (HPLC) with UV detection, from a standard incubation mixture containing 3 mM ATP. Orchidectomy, performed 4 weeks before sacrifice, decreased ATPase activity of MBH. Testosterone propionate treatment (50 micrograms/day X 2 days) to castrated animals resulted in a 4-fold increase in enzyme activity in the POSC, an effect that might be related to the behavioral effects of androgens. None of the treatments seemed to influence the enzyme activity of the cerebral cortex.

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.

Repeated PGE1 treatment enhances nitric oxide and erection responses to nerve stimulation in the rat penis by upregulating constitutive NOS isoforms.

PURPOSE To assess whether intracavernosal injections of prostaglandin E1 (PGE1) can influence nitric oxide (NO) release in the corpora in a rat model of penile erection. MATERIALS AND METHODS The extracellular levels of NO were monitored at 100 seconds intervals in the corpus cavernosum of anesthetized rats by using differential normal pulse voltammetry with porphyrin-Nafion coated carbon fiber microelectrodes. The intracavernosal pressure (ICP) was simultaneously recorded. PGE1 was given either as a single dose (ranging from 0.2 to 15 microg.) or as repeated 2 microg. injections in alternate days for two weeks. The NO and ICP responses to electrostimulation of the cavernosal nerve (SCN) was studied in the animals in the repeated treatment schedule at 1, 7, 15 and 30 days after its termination. The levels of the three NO synthase (NOS) isoforms in the cavernous tissue were measured by immunoblotting. RESULTS Acute PGE1 treatment dose-relatedly increased NO levels in the corpora, with a concomitant ICP increase with the highest dose. Repeated 2 microg. PGE1 injections increased the NO and ICP responses to SCN as compared with intact or vehicle-injected animals. This treatment also increased the penile content of the neuronal and endothelial NOS proteins. The inducible NOS isoform remained unchanged after either vehicle or PGE1 injections. The effects of the repeated PGE1 treatment were greater in the group studied 24 hours after the last injection and decreased progressively thereafter. CONCLUSIONS Stimulation of NO release can contribute to the erectogenic effect of intracavernous PGE1 injections. The increased levels of constitutive NOS isoforms in the corpora could contribute to the improvement of the erectile function reported by some patients following repeated treatment with vasorelaxant agents.