Biomedical subjects

R G Paredes

Publications and source records attributed to R G Paredes.

At least 19 recordsLinked to original sources

PubMed2007

Neuronal activity of aromatase enzyme in non-copulating male rats.

There are apparently normal male rats that fail to initiate copulation; these animals are called non-copulating (NC) males. Several research groups have demonstrated that conversion of testosterone to oestradiol (aromatisation) in specific brain areas known to be involved in the control of masculine sexual behaviour is fundamental in the control of masculine sexual behaviour. The aim of the present study was to test the hypothesis that the concentration of aromatase activity (AA) in the brain is lower in NC males than in copulating males (C). We quantified AA in several brain nuclei and also evaluated whether NC rats have altered concentrations of testosterone in their plasma. We found that AA was reduced in the medial preoptic nuclei (MPN) of NC male rats vs C males. In addition, NC and C male rats had similar plasma levels of testosterone. These data suggest that reduced levels of AA in the MPN could be a crucial factor associated with lack of male coital behaviour in rats.

Animals↗

PubMed2006

Kindling increases aversion to saccharin in taste aversion learning.

Kindling is a model in which an initially subconvulsive electrical stimulation of certain brain areas eventually develops a generalized seizure that produces behavioral and long term neuronal changes. In the present study we evaluated if kindling can modify conditioning taste aversion (CTA). In this paradigm animals acquire aversion to saccharin when it is presented as the conditioned stimulus (CS) followed by an injection of lithium chloride (LiCl) that induces a gastric irritation as the unconditioned stimulus (US). Male Wistar rats were implanted with bipolar electrodes aimed at the right amygdala (AMG) or at the right insular cortex (IC). The animals were stimulated daily until they reached stages 2-4 (intermediate) or until kindling was fully established (three consecutive stage 5 seizures). At least two weeks after kindling stimulation had ceased the animals were deprived of water for 24 h and given 10-min drinking sessions twice a day for 4 days. On day 5 (morning session) tap water was replaced by saccharin solution (0.1%), 20 min later the animals were injected with LiCl (7.5 ml/kg i.p., 0.2 M) to induce gastric malaise or taste aversion. After three more days of baseline consumption, water was substituted by a fresh 0.1% saccharin solution to test the aversion. AMG-kindling delayed the extinction of CTA. Animals with kindling in the IC had a higher retention than the sham kindling group; that is, they drank significantly less saccharin solution than the other groups. The results of the present experiment show that local modification of brain function induced by kindling stimulation can prolong the aversive effects of CTA.

Amygdala↗

PubMed2006

The role of the dorsolateral tegmentum in the control of male sexual behavior: a reevaluation.

The medial preoptic area/anterior hypothalamus (MPOA/AH) plays a key role in the control of male sexual behavior. Independently of the type, MPOA/AH lesions permanently eliminate male sexual behavior in the rat. The MPOA/AH projects among other structures to the dorsolateral tegmentum (DLT). Bilateral electrolytic lesions of the DLT or the unilateral electrolytic destruction of the MPOA/HA combined with a contralateral electrolytic lesion of the DLT eliminate male sexual behavior. In the present experiment, we evaluated if neurotoxic lesions of the DLT produce the same behavioral deficits as those observed after electrolytic lesions. This would allow us to evaluate if neurons of the DLT or the fibers passing through this area are important in the control of male sexual behavior. To this aim, sexually experience male rats were tested for socio-sexual behavior, partner preference and motor execution in order to determine if the possible behavioral changes could be attributed to alterations in sexual motivation or motor execution. One week after the bilateral DLT lesions the animals were evaluated in the same behavioral tests. The lesions were identified by glial fibrillary acidic protein (GFAP) and neuronal nuclear protein (Neu-N) immunohistochemistry. No significant consistent effects upon sexual behavior were observed in any of the groups, including the group with clear bilateral damage of the DLT. A reduction in the percentage of males displaying ejaculation in the first post-lesion test was observed for all groups injected with quinolinic acid. No effects upon partner preference or motor coordination were observed after the lesion in any of the groups. The lack of effect of DLT neurotoxic lesions upon mating suggests that neurons of this structure are not involved in the control of male sexual behavior.

Analysis of Variance↗

PubMed2006

Comparative analysis of immunoreactive cells for androgen receptors and oestrogen receptor alpha in copulating and non-copulating male rats.

In some species, including gerbils, guinea pigs, mice, rams and rats, some apparently normal males fail to mate. These kinds of animals have been named 'noncopulating (NC)'. The cause of this behavioural deficit is unknown. The present study aimed to determine whether NC male rats have alterations in the amount of androgen (AR) and oestrogen receptor alpha (ERalpha) in a neuronal circuit important for the control of male sexual behaviour; the vomeronasal projection pathway. We evaluated the number of AR and ERalpha immunoreactive (AR-IR and ERalpha-IR) cells in the accessory olfactory bulb (AOB), the bed nucleus of the stria terminalis (BNST), the anterior-dorsal medial amygdala (MeAD), the posterior dorsal amygdala (MePD) and the medial preoptic area (MPOA). The results demonstrate that the number of AR-IR cells in NC males was significantly higher compared to copulating (C) males in the MePD, but no significant differences were found in any of the other structures analysed. ERalpha-IR cells were more abundant in NC than in C males in the MeAD and the MePD. However, in the MPOA the number of ERalpha-IR cells was significantly reduced in NC males. No significant differences were found in the AOB or in the BNST. A similar pattern of results was observed when regions within these structures that are activated by Fos expression, on mating or exposure to sexually relevant cues were analysed. The differences in the number of AR and ER in particular brain areas could be associated with alterations in sexual behaviour as well as partner and olfactory preference for receptive females seen in NC male rats.

Animals↗

PubMed2005

Olfactory preference and Fos expression in the accessory olfactory system of male rats with bilateral lesions of the medial preoptic area/anterior hypothalamus.

In the present study we evaluated if a medial preoptic area/anterior hypothalamus lesion affects the olfactory preference toward soiled bedding from receptive females in comparison to bedding from anestrous females or clean bedding. In the second part of the study we evaluated the accessory olfactory system response to estrous bedding with Fos immunoreactivity to determine if the preoptic lesions modify the processing of sexually relevant olfactory cues. Before medial preoptic area/anterior hypothalamus lesions, male rats spent more time investigating estrous bedding as opposed to anestrous or clean bedding. After the lesion, subjects showed no preference between estrous and anestrous bedding; that is, males spent the same amount of time investigating both types of bedding. These two odors were investigated more than clean bedding. Increments in Fos immunoreactivity neurons were seen in structures of the accessory olfactory system after exposure to soiled estrous bedding [granular layer of the accessory olfactory bulb, anterior-dorsal medial amygdala, posterior-dorsal medial amygdala, bed nucleus of the stria terminalis]. These results suggest that bilateral destruction of the medial preoptic area/anterior hypothalamus modify male olfactory preference in such a way that subjects spend the same time smelling and investigating bedding from estrous and anestrous females. This change in olfactory preference is not associated with alterations in the processing of sexually relevant olfactory cues by the accessory olfactory system.

Animals↗

PubMed2001

Combined mesencephalic and hypothalamic transplants reverse lesion-induced sexual behavior deficits in the male rat.

Studies of sexual behavior in rodent animal models have provided evidence about the relevant role played by the medial preoptic area of the anterior hypothalamus and the central tegmental field within the mesencephalon in the control of this behavior. Bilateral lesions of the anterior hypothalamus or central tegmental field as well as combined unilateral lesions of both these regions result in sexual behavior deficits. Studies using fetal hypothalamic transplants have been shown to reverse sexual behavior deficits induced either by lesions or aging. However, no previous study has evaluated the effect of combined homotopic transplants into both the anterior hypothalamus and the mesencephalon. In the present study male Wistar animals received two electrolytic lesions, one aimed at the ipsilateral medial preoptic area of the anterior hypothalamus and the other at the contralateral central tegmental field. Following these lesions, unilateral homotopic fetal hypothalamic and mesencephalic transplants were placed into the lesioned areas. Sexual behavior recovered gradually and by weeks 14-15 after transplantation, above 90% of animals with bilateral transplants showed mounts, intromissions, and ejaculations. Only animals with viable transplants located within both lesioned areas showed recovery. These results indicate that the behavioral deficits induced by combined unilateral lesions of hypothalamic and mesencephalic regions can be reversed by homotopic fetal transplants and that this recovery could be the result of the restoration of a behavioral relevant circuit between transplants and host brain nuclei separated by as much as 5 mm, which makes this an excellent model to study mechanisms underlying behavioral recovery after transplantation.

Animals↗

PubMed2001

Only self-paced mating is rewarding in rats of both sexes.

When rats are mated in a traditional mating chamber (with one male and one female) in which the male dictates the pace of the copulatory sequence, males develop a reward state as evaluated by conditioned place preference (CPP). In this mating situation no reward state is induced in females. However, when female rats are able to control (pace) the rate of sexual stimulation, thereby reducing the aversive consequences associated with mating, a clear CPP is observed. In the present study the CPP paradigm was used to determine whether if the reinforced state induced by coital interactions in male rats can be maintained when females pace the sexual interaction. Adult male and female rats were mated in one of two different conditions: (1) where subjects were able to pace their coital interactions or (2) where subjects were not able to pace their sexual contacts. The results showed that when males had control over the sexual interaction they developed a clear place preference while males that mated with females that paced their coital contacts did not develop CPP. Similarly, only females that were able to pace their sexual contacts developed place preference. These results suggest that coital interactions in males, as well as in females, can induce a reward state only when they are able to control the sexual interaction. Under seminatural conditions sexual behavior in rats is highly promiscuous, they mate in groups and repeatedly change partners in the middle of copulation. This behavioral sequence allows both, male and female to control the rate of sexual interaction, assuring the induction of a reward state outlasting the actual performance of coital responses.

Animals↗

PubMed2001

Naloxone blocks place preference conditioning after paced mating in female rats.

Sexual behavior in male rats induces a positive affect as evaluated by conditioned place preference (CPP). In addition, when females control or "pace" the rate of sexual interaction, a clear CPP is also observed. The reward state induced by mating in male rats is blocked by the injection of the opioid antagonist naloxone. In the present experiment, a dose of 4 mg/kg of naloxone completely blocked the CPP induced in females by paced mating. It appears that a common opioid system is involved in the positive affect induced by sexual behavior in both male and female rats.

Animals↗

PubMed2000

Serotonin and sexual behavior in the male rabbit.

Sexual behavior was evaluated in sexually experienced male rabbits after the administration of different serotonergic drugs. The serotonin1A receptor agonist 8-OH-DPAT, 1 mg/kg, inhibited male rabbit sexual behavior when animals were tested 15 min after subcutaneous (SC) administration of this compound. Lower doses, 0.25 and 0.5mg/kg, were ineffective at a test 30 min after drug injection. Furthermore, 8-OH-DPAT, 0.25mg/kg, failed to revert the inhibitory effects upon sexual behavior produced by lidocaine application to the rabbit penis. Stimulation of 5-HT1B/2C receptors by TFMPP, at doses between 0.625 and 2.5 mg/kg, produced a drastic inhibition of sexual behavior when the drug was administered SC 30 min before behavioral observation. Doses below 5mg/kg were ineffective when given intraperitoneally 15 min before test. When the 5-HT1D/2C receptors were stimulated by the agonist mCPP a reduced number of mounts and ejaculations was observed after the SC administration of 1.25 and 2.5 mg/kg. Similarly, the mixed 5-HT agonist/antagonist lisuride reduced the percentage of rabbits displaying mounting behavior at doses of 0.25 and 0.5 mg/kg SC. All compounds tested produced a clear inhibition of male rabbit sexual behavior independently of the receptor subtype activated. These results are at variance with previous observations in rats where 8-OH-DPAT and lisuride produced a drastic facilitation of masculine coital behavior. Moreover, while the inhibition of male sexual behavior in rats produced by TFMPP and mCPP is associated with a disruption of the execution of this behavior, in rabbits these compounds reduced sexual motivation. These results indicate that the effects of serotonergic drugs on sexual behavior are species specific.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2000

Can a generalized kindling seizure induce a reward state?

The postictal behavioral depression (PBD), characterized by behavioral immobility and unresponsiveness to environmental stimuli, observed after a stage 5 kindling seizure is opioid dependent. Morphine injection prolongs while naloxone and naltrexone (opioid antagonists) reduce or eliminate PBD. Opioids have clear rewarding actions that can be easily detected by place preference conditioning (PPC). In the present study, we evaluated if the opioid release after a stage 5 kindling seizure that produces PBD could induce PPC. Male rats were kindled in the medial preoptic area (MPOA), the amygdala (AMG) or insular cortex (IC). After kindling was established their initial preference in a three-compartment chamber was determined. During conditioning, subjects received a standard kindling stimuli that evoked a stage 5 seizure. At the end of the after discharge and during the PBD the animals were placed in the non-preferred chamber for 30 min. On alternate days they were placed without stimulation in the preferred chamber. At the end of conditioning the kindled groups showed a clear change of preference. This change of preference was completely blocked by injection of naloxone. These results suggest that opioid release after a stage 5 kindling seizure can induce a positive affect of sufficient intensity and duration to induce conditioning.

Amygdala↗

PubMed1999

What do female rats like about sex? Paced mating.

The motivational aspects of female sexual behavior have been evaluated by a variety of methodologies including: the increasing barrier method, the runway procedure, partner preference test, operant behavior and conditioned place preference. When female rats are tested for sexual receptivity under traditional laboratory conditions, usually a small open area, both appetitive and aversive components of the sexual interaction are easily observed. For example, after prolonged testing, subsequent lordosis and the intensity of this response are reduced increasing the rejection behavior by the female. However, when female rats are allowed to pace (control) the rate of sexual stimulation they received, as usually occurs under seminatural and natural conditions, the aversive properties of mating are reduced. The conditioned place preference can be use to measure the positive affect elicited by mating. We have combined pacing and conditioned place preference in an attempt to reduced the possible aversive consequences associated with mating and increase the likelihood of detecting the appetitive effects of coital interaction in female rats. Only female rats that regulated (paced) their coital interactions with a stud male through a two-compartment chamber in which only the female could freely move from one compartment to the other developed a clear place preference. As well, females that received ten or 15 paced intromissions (without ejaculation) also developed place preference. The place preference induce by paced mating is blocked by the systemic administration of naloxone suggesting that opioids are involved in the reward processes associated with paced mating. Paced sexual interactions can induce a positive affect of sufficient intensity and duration to induce conditioning.

Animals↗

PubMed1998

Lesions of the medial preoptic area/anterior hypothalamus (MPOA/AH) modify partner preference in male rats.

When given the choice, male rats will interact with a receptive female while female rats will interact with a sexually active male. In the present experiment partner preference was tested in male and female rats before and after lesions of the medial preoptic area of the anterior hypothalamus (MPOA/HA). Subjects were gonadectomized, treated for 10 days with 5 microgram/kg of estradiol benzoate (EB) and tested for male coital behavior with receptive females and for partner preference in a three compartment box with free access to either a sexually receptive female or a sexually active male. The same tests were repeated after 10 days of treatment with 5 mg/kg of testosterone propionate (TP). The subjects then received a bilateral electrolytic lesion aimed at the MPOA/AH. Two weeks after the lesion the hormonal treatments and behavioral tests were repeated in the same sequence. Prior to the lesion, females showed a clear preference to interact with the stimulus male while male subjects showed a preference to interact with the receptive female regardless of the hormonal treatment they received. After lesions the females preference for the opposite sex was not modified, they spent more time in the chamber with the stimulus male regardless of whether they had an extensive bilateral destruction of the MPOA/AH or a sham lesion. Males with bilateral destruction of the MPOA/AH changed their partner preference after the lesion. They spent significantly more time in the chamber with the stimulus male than in the chamber with the receptive female. As well, the coital behavior of males with bilateral destruction of the MPOA/AH was significantly reduced after the lesion. The change of preference was observed when the lesioned animals were treated either with EB or TP. The results of the present experiment further support the notion that the MPOA/AH is a crucial structure in the integration of sensory cues that determine partner preference.

Analysis of Variance↗

PubMed1998

Testosterone augments neuronal Fos responses to estrous odors throughout the vomeronasal projection pathway of gonadectomized male and female rats.

Pheromonal signals emanating from female rats' soiled bedding have previously been shown to attract male conspecifics and to augment the number of Fos-immunoreactive neurons present in portions of the vomeronasal projection pathway, ranging from the accessory olfactory bulb (AOB) to the medial preoptic area (mPOA) of gonadectomized, testosterone-treated male as well as female subjects. In the present study we extended these findings by showing that these neuronal Fos responses to estrous odors occurred only in gonadectomized subjects which received testosterone propionate (TP), as opposed to oil vehicle, at the time of testing. Previously, when treated with TP, all subjects had displayed mounting with an estrous female. In subsequent tests, gonadectomized male and female subjects spent significantly more time investigating soiled estrous bedding as opposed to clean or anestrous bedding, again, provided they were receiving TP. We propose that testosterone facilitates odor-induced neuronal Fos expression either via its conversion to estradiol, and the subsequent action of this steroid at estrogen response elements on the c-fos gene, or via some indirect mechanism involving centrifugal control of AOB neurotransmission. The ability of female odors to stimulate equivalent numbers of Fos-IR cells in gonadectomized, TP-treated male and female rats indicates that the functional responsiveness of neurons throughout the vomeronasal projection pathway is made more male-like by the fetal actions of testosterone in female as well as in male rats. Previous studies established that males have more neurons than females in several segments of the vomeronasal pathway; however, this morphological sexual dimorphism does not account for the observed isomorphic neuronal Fos responses to female odors.

Animals↗

PubMed1998

Socio-sexual behavior in male rats after lesions of the dorsolateral tegmentum.

The medial preoptic area of the anterior hypothalamus (MPOA/AH) and the dorsolateral tegmentum (DLT) play an important role in the control of sexual behavior. Unilateral lesions of the MPOA/AH (medial preoptic area of the anterior hypothalamus) combined with unilateral lesions of the contralateral DLT result in deficits in male sexual behavior, while bilateral electrolytic lesions of the DLT have similar effects. In the present study, coital and socio-sexual interactions were recorded before and after bilateral electrolytic DLT lesions. Coital behavior was monitored for 15 weeks after surgery and socio-sexual interactions one 1 and 3 weeks after lesion. DLT-lesioned animals showed reduced copulatory behavior throughout the 15 weeks postlesion. This inhibition was associated with changes in exploratory (sniffing), precopulatory (pursuit and genital exploration), and postcopulatory behaviors (self-grooming). No differences were found in the weights of the testicles, prostate and seminal vesicles. These results indicate that lesions of the DLT produced permanent deficits in sexual behavior associated with a generalized modification of sociosexual behavior. These deficits indicate reduced sexual motivation possibly due to the disruption of the output pathway from the MPOA/AH (medial preoptic area of the anterior hypothalamus) to the DLT.

Animals↗

PubMed1998

GABAergic drugs and sexual behaviour in the rabbit: evidence for species-specific effects.

The effects of gamma-amino butyric acid (GABA)-ergic drugs on male rabbit sexual behaviour have been evaluated. The GABA(A) agonist 4,5,6,7-tetrahydroxixazolo-5,4c-pyridin-3-ol (THIP), the GABA(B) agonist R-baclofen and the GABA antagonists picrotoxin and bicuculline were used. Injection of THIP, 20 mg/kg, s.c. produced a complete suppression of sexual behaviour and R-baclofen, 2.5 mg/kg, s.c. a significant inhibition. Intraperitoneal injections produced effects at higher doses than did s.c. injections. The inhibition produced by R-baclofen was associated with strong motor effects as shown by the water escape test. It is probable, therefore, that the reduced sexual behaviour observed after treatment with this drug is a consequence of sedative or muscle relaxant effects. By contrast, the dose of THIP that inhibited sexual behaviour had no effect on the water escape test. These results show that the GABA(A) agonist inhibits sexual behaviour in the male rabbit independent of effects on the motor system. The GABA antagonists had marginal or no effects on sexual behaviour. When these data are compared to previous results in the rat, substantial differences are seen. As there are differences between the effects on rat and rabbit sexual behaviour by other types of drugs, it appears that drug action on sexual behaviour cannot be generalized from one species to another.

Animals↗

PubMed1997

The inhibitory effects on sexual behavior and ambulatory activity of the mixed GABAA/GABAB agonist progabide are differentially blocked by GABA receptor antagonists.

Progabide inhibited male rat sexual behavior at a dose of 200 mg/kg. This dose had only modest effects on ambulatory activity and no effect at all on motor coordination as evaluated by a rotarod test. The GABAA antagonist bicuculline, at a dose of 1 mg/kg, blocked the effects of progabide on sex behavior. In contrast, the GABAB antagonist CGP 35348, at doses of 50 and 100 mg/kg, was ineffective. These doses have previously been shown to block the actions of baclofen on sexual behavior. It was concluded that the GABAA but not the GABAB receptor is important for the inhibitory effects of progabide on that behavior. The actions of progabide on ambulatory activity were not blocked by bicuculline or CGP 35348 at any of the doses used (up to 2 and 200 mg/kg, respectively). Even the combination of both antagonists was ineffective. This suggests that the motor effects of progabide are mediated by either a non-GABAergic receptor or by a subtype of the GABAA or the GABAB receptor that is not sensitive to the antagonists. Present results show that the effects of progabide on motor functions depend on mechanisms different from those involved in its effects on sexual behavior. They further suggest that the GABAA receptor may be important for drug actions on male sexual behavior.

Animals↗

PubMed1997

GABAergic drugs and socio-sexual behavior.

To elucidate the role of GABA in the control of sexual behavior, the effects of the GABA(A) agonist 4,5,6,7-tetrahydroisoxazolo[5,4c]-pyridin-3-ol (THIP), the GABA transaminase inhibitors sodium valproate and gamma-acetylen-GABA (GAG), and the GABA synthesis inhibitors isoniazide and deoxypyridoxine were evaluated in sexual behavior, exploration, and sociosexual interactions with a receptive female or a castrated male. Furthermore, to discriminate possible general inhibitory effects from those specific to sexual behavior, the doses of the drugs that produced a significant inhibition of copulation were tested in a free drinking procedure. THIP (16 mg/kg), sodium valproate (400 mg/kg), GAG (100 mg/kg), and deoxypyridoxine (400 mg/kg) produced a strong inhibition of sexual behavior. The percentage of animals displaying mounts and intromissions as well as the mean number of mounts and intromissions were significantly reduced. Sociosexual interactions with a receptive female or a castrated male and exploratory behaviors were also reduced. The most consistent effects observed were reductions in sniffing, self-grooming, and rearing. Drinking behavior was significantly reduced in doses that inhibited sexual behavior. These results further support the hypothesis that altered GABAergic neurotransmission produces reduced sensitivity to environmental stimuli and thereby inhibits sexual and drinking behavior in a nonspecific way.

Animals↗

PubMed1997

Sexual behavior regulated (paced) by the female induces conditioned place preference.

The possibility that female-paced coital behavior induces a reward state of sufficient intensity and duration to induce conditioning was evaluated by the conditioned-place-preference paradigm. Ovariectomized female rats, treated with estradiol benzoate and progesterone, regulated (paced) their coital interactions with a stud male through a 2-compartment chamber in which only the female could freely move from one compartment to the other. The females that paced their coital interactions showed a clear place preference. In contrast, no change in preference was observed in the females that could not pace their coital contacts. The change in preference in the females that paced their coital interactions was similar to that produced by an injection of morphine (1 mg/kg). These results suggest that coital interactions in females can induce a reward state when the females can control the pace of the sexual interaction.

Animals↗