Michal Bialy

Precontact 50-kHz vocalizations in male rats during acquisition of sexual experience.

50-kHz ultrasonic vocalizations emitted by male rats during a 5-min period before introduction of a female (precontact vocalizations [PVs]) were analyzed in the context of acquisition of sexual experience. Changes in the main copulatory parameters and their N-methyl-D-aspartate (NMDA) receptor dependence, the role of contact with either anestrous or estrous females, and conditioning to odor and background cues were also investigated. Mount latency (ML) and intromission latency (IL) decreased after the 1st copulatory session, but ejaculation latency (EL) changed significantly only starting from the 4th session onward. The number of PVs gradually increased during the first 3-4 sessions. Blocking of NMDA receptors affected PVs and EL but not ML or IL. After a 5-month break in copulatory sessions, ML remained unchanged, whereas EL increased and the number of PVs decreased significantly. PVs were most robustly elevated by contact with estrous females. Exposure to background cues resulted in a linear decrease in number of PVs during 10 subsequent sessions without exposure to a female. The results suggest that, in the course of acquisition of a sexual experience, PVs reflect a learning process that depends on a rewarding value of sociosexual contact.

Sexual behavior in male rats after nitric oxide synthesis inhibition

The influence of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) on the copulatory behavior of sexually experienced male Wistar rats was investigated. L-NAME was injected i.p. 10 min before the onset of a session using a dose of 30 mg/kg (L-NAME 30 group), or 60 mg/kg (L-NAME 60 group). The copulatory sessions were terminated after the third ejaculation in the control group or after 1500 s in the L-NAME 30 and L-NAME 60 groups. L-NAME administration reduced the number of rats that achieved ejaculation by 43% and 86% in the L-NAME 30 and 60 groups, respectively. In both experimental groups only a few intromissions and an increased number of mountings were observed. An increase in the number of ultrasonic vocalizations in the 50 kHz band, a dose-dependent effect, was observed. The level of sexual motivation evaluated by mount latency was not influenced by inhibition of NO synthesis.

Delayed c-fos expression in sensory cortex following sexual learning in male rats

An elevated expression of c-fos protooncogene, encoding transcription factor Fos, is known to serve as a useful marker of neuronal activation. In the studies reported in this communication we have used Northern and dot blot techniques to analyze c-fos mRNA levels in male rat brain during the learning of the copulatory behavior. The animals were trained (single ejaculation in a training/testing session) for up to 7 sessions. C-fos mRNA levels have been found to increase in the sensory cortex area following the third and fifth session but not after the first and the last one.

Effects of D1 receptor agonist SKF 38393 on male rat sexual behavior and postcopulatory departure in the goal compartment–runway paradigm

Male rats were tested in an apparatus in which the goal compartment of the runway was connected with the start compartment by a one-way door. In this apparatus, the male spontaneously left the goal compartment containing the estrous female after a mount bout (the cluster of one or more copulatory events) and a new run started. This effect (the postcopulatory departure) seems to be due to the competition between the incentive value of the stimulus female and the runway. The dopamine D(1) receptor agonist SKF 38393 at the doses of 1-5 mg/kg sc significantly prolonged the time spent by the male in the goal compartment, while both run latency and run duration remained unaffected. Further analysis showed that the prolongation of the time in goal compartment results from increased duration of copulatory behavior accompanied by increased number of copulatory events. Although SKF 38393 did not influence the latency of postcopulatory departures, incomplete departures occurred in five out of eight males. In the free access to female conditions, the SKF 38393 did not influence copulatory performance, except for a reduction in the number of intromissions at the dose of 1 mg/kg sc. On the other hand, a significant reduction of postejaculatory ultrasonic vocalization was observed.

D1 receptors involved in the acquisition of sexual experience in male rats

As we found previously, changes in ultrasonic vocalizations in the 50-kHz band emitted before a female is introduced into a copulatory chamber (precontact vocalizations-PVs) and shortening of ejaculation latency (EL) in subsequent copulatory sessions are correlated and reflected acquisition of sexual experience in male rats. In the present experiments, we investigate the role of the D1 receptor in this phenomenon. First, the effects of a D1 antagonist and D1 agonists injected subcutaneously during the first sexual contacts were analyzed. The antagonist (SCH-23390) inhibited changes in PVs and EL as well as rearing (R) and mount latency (ML). Both agonists (SKF-38393 and selective SKF-82957) inhibited PVs also at doses where no effects on EL and ML were observed. Repeated injections of five agonists, with or without socio-sexual contacts, had an effect on later PVs and R (long-term effect) but not on copulatory performance during the subsequent four sessions. In the last experiment, a D1 agonist (SKF-82957, 0.5 microg) was injected bilaterally into nucleus accumbens (N.Acc) before each of the first five sessions. The D1 agonist in N.Acc facilitated initiation of copulation in treatment-naïve rats. Repeated administration of the D1 agonist into the brain had long-lasting effects on PVs, R and ML, probably as a result of long-term changes in neuronal structures involved in acquisition of sexual experience, in this part of the nucleus accumbens. Repeated D1 agonist administration probably inhibits/reverses sensitization processes in dopamine structures. The results indicate a role of D1 receptors in acquisition of socio-sexual experience and suggest independent neuronal pathways for changes in PVs and EL.

Blockade of androgen receptor in the medial amygdala inhibits noncontact erections in male rats

Our previous work demonstrated that androgens in the medial amygdala (MeA) of castrated male rats maintained noncontact erections (NCEs), which occur during exposure to an inaccessible receptive female, for one week after implantation. The present experiments investigated the effects of implantation into the MeA of either flutamide (F), a blocker of androgen receptors, or of 1,4,6-androstatrien-3,17-dione (ATD), which blocks aromatization of testosterone. One day after implantation of F, fewer males displayed NCEs, and had longer latencies to the first NCE and fewer NCEs, and spent less total time in genital grooming, compared to the control group. ATD had only weak facilitative effects on some measures of NCEs. These results suggest that androgen receptors in the MeA play a major role in the regulation of NCEs and that the MeA is one of the neuronal structures that regulate male sexual arousal. Furthermore, it is sensitive to relatively fast changes in the level of androgen receptors stimulation.

Sexual performance and precontact 50-kHz ultrasonic vocalizations in WAG/Rij rats: effects of opioid receptor treatment.

WAG/Rij rats are genetically selected animals that model absence epilepsy in rats. Ultrasonic vocalizations and sexual behavior - both ethologically relevant markers of reward system functioning - are poorly described in this strain. The aim of our experiment was to investigate reward-dependent precontact 50-kHz vocalizations (PVs) and copulatory behavior as well as the effects of opioid receptor treatment on such behaviors in sexually experienced WAG/Rij males and rats from two control strains: Sprague-Dawley and Crl: Han Wistar. We analyzed the effects of the opioid receptor antagonist naltrexone (3 mg/kg) and the agonist morphine (1 mg/kg) administration. Additionally, we analyzed the initiation of copulation in sexually naïve males before drug treatment. A significantly lower number of sexually naïve WAG/Rij rats initiated copulation. Sexually experienced WAG/Rij males differed at the control session (after physiological saline treatment) compared with Sprague-Dawley rats: WAG/Rij rats displayed more 50-kHz precontact vocalizations and had longer mount and intromission latencies, longer ejaculation latency, longer postejaculatory latency to exploration, longer 22-kHz vocalization duration after ejaculation, and longer postejaculatory intromission latency. Compared with Crl: Han Wistar rats, WAG/Rij males displayed longer mount latency and shorter 22-kHz vocalization duration. Neither naltrexone nor morphine affected PVs in all groups. On the other hand, opioid receptor treatment differently influenced the number of intromissions required to achieve ejaculation and 22-kHz postejaculatory vocalization duration in WAG/Rij rats than in both control groups. This suggests functional differences in the opioid system in this strain. As a result of the number of males that initiated copulation as well as the number of intromissions to ejaculation and 22-kHz postejaculatory vocalizations which all depend on D1 receptor activation, we suggest that the proportion of opioid receptor to D1 receptors in WAG/Rij rats is different when compared with the control strains. The reward system of Wag/Rij rats with absence epilepsy is sensitive to social rewards (high level of precontact 50-kHz ultrasounds) although this strain displays a lower level of sexual motivation (longer mount latency) compared with other control strains. A lower number of sexually naïve rats initiating copulation and longer mount latency in sexually experienced males could suggest a moderate depressive-like syndrome in this strain of rats.

Common Genetic Variants Link the Abnormalities in the Gut-Brain Axis in Prematurity and Autism

This review considers a link between prematurity and autism by comparing symptoms, physiological abnormalities, and behavior. It focuses on the bidirectional signaling between the microbiota and the brain, here defined as the microbiota-gut-vagus-heart-brain (MGVHB) axis and its systemic disruption accompanying altered neurodevelopment. Data derived from clinical and animal studies document increased prevalence of gastrointestinal, cardiovascular, cognitive, and behavioral symptoms in both premature and autistic children and suggest an incomplete maturation of the gut-blood barrier resulting in a “leaky gut,” dysbiosis, abnormalities in vagal regulation of the heart, altered development of specific brain regions, and behavior. Furthermore, this review posits the hypothesis that common genetic variants link the abnormalities in the MGVHB axis in premature and autistic pathologies. This hypothesis is based on the recently identified common genetic variants: early B cell factor 1 (EBF1), selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC), and angiotensin II receptor type 2 (AGTR2), in the maternal and infant DNA samples, associated with risk of preterm birth and independently implicated in a risk of autism. We predict that the AGTR2 variants involved in the brain maturation and oxytocin-arginine-vasopressin (OXT-AVP) pathways, related to social behavior, will contribute to our understanding of the link between prematurity and autism paving a way to new therapies.