Antidepressants, Sexual Behavior, and Translational Models for Male Sexual Dysfunction: Development of Animal Models, Pharmacology, and Genetics

Olivier, Jocelien; Janssen, Josien; Pattij, Tommy; Prêtre, Stephen De; Olivier, Berend

doi:10.1007/978-1-0716-2083-0_20

Cited by 3 publications

(6 citation statements)

References 220 publications

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“…We postulate that the paroxetine/Atlas987 combination creates a new approach to on-demand treatment of lifelong Premature Ejaculation. The male rat model used has been extensively used by us ( Bijlsma et al, 2014 ) and has been developed as predictive for rapid ejaculating rats that reflect a rat homolog of a human male with premature ejaculation ( Pattij et al, 2005 ; Olivier et al, 2006 , 2022 ). When testing male rats weekly during 30 min-tests against an estrus female each rat develops his own sexual (endo)phenotype after 5 or more successive tests ( Olivier et al, 2017 ; Esquivel-Franco et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…We trained 32 male rats extensively by weekly tests in which each male was tested 30 min against a female in estrus, showing proceptive and receptive sexual behavior ( Olivier et al, 2006 ; Bijlsma et al, 2014 ; Snoeren et al, 2014 ; Heijkoop et al, 2018 ; Huijgens et al, 2021 ). Rats trained this way gain an individual and stable level of sexual behavior after 4–7 tests (measured by the number of ejaculations/test and the first ejaculation latency; Olivier et al, 2022 ). We selected male rats with a normal to high level of sexual activity (2–5 ejaculations in the 30-min test) for our pharmacological experiments as described before ( Pattij et al, 2005 ; Chan et al, 2008 ).…”

Section: Methodsmentioning

confidence: 99%

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A new approach to ‘on-demand’ treatment of lifelong premature ejaculation by treatment with a combination of a 5-HT1A receptor antagonist and SSRI in rats

Olivier,

Janssen,

Esquivel-Franco

et al. 2023

Front. Neurosci.

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Lifelong premature ejaculation (PE) in men lacks an adequate on-demand pharmacological treatment. Although selective serotonin reuptake inhibitors (SSRIs) are used for PE they only work after chronic treatment, or if used on-demand, less adequately than chronic SSRI treatment. It has been shown that the addition of a behaviorally silent 5-HT1A–receptor antagonist to an SSRI can generate acute inhibitory effects on male rat sexual behavior. Atlas987 is a selective 5-HT1A-receptor antagonist with equal potency to displace agonist and antagonist binding to pre- and post-synaptic 5-HT1A receptors in rat and human brain. To investigate whether Atlas987 together with the SSRI paroxetine, a combination called Enduro, induces acute inhibitory effects on male rat sexual behavior, we tested Enduro in Wistar rats in a dose-dependent manner. We first tested the 5-HT1A receptor antagonist Atlas987 in 8-OH-DPAT induced serotonergic behavior in rats. Second, we tested Enduro in a dose-dependent manner in male sexual behavior. Third, we tested the effective time window of Enduro’s action, and lastly, we measured the plasma levels of Atlas987 and paroxetine over an 8-h period. Results showed that Enduro acutely and dose-dependently reduced the number of ejaculations and increased the ejaculation latencies. The behavioral pattern induced reflected a specific effect on sexual behavior excluding non-specific effects like sedation or sensoric-motoric disturbances. The time-window of activity of Enduro showed that this sexual inhibitory activity was at least found in a 1–4 h’ time window after administration. Plasma levels showed that in this time frame both Atlas987 and paroxetine are present. In conclusion, in rats, Enduro is successful in acutely inhibiting sexual behavior. These results may be therapeutically attractive as “on demand” treatment for life-long premature ejaculation in men.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A new approach to ‘on-demand’ treatment of lifelong premature ejaculation by treatment with a combination of a 5-HT1A receptor antagonist and SSRI in rats

Olivier,

Janssen,

Esquivel-Franco

et al. 2023

Front. Neurosci.

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“…Additionally, this model may be seen as useful in pharmacological and neurobehavioral experiments to evaluate the potential influence of various agents on sexual parameters, which includes selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, antipsychotic drugs, other 5-HTr modulators, dopamine receptor agents, autonomic nervous system agents, phosphodiesterase inhibitors, nitrates, other types of endogenic substances, and toxic factors ( Olivier et al, 2006 , 2017 , 2022 ; Lin et al, 2015 ; Sanna et al, 2015 ; Chiang and Park, 2020 ; Esquivel-Franco et al, 2020 ; Kermath et al, 2022 ). Similarly, it could be useful in investigations of emotional responses, in addition to models of erectile dysfunction or premature ejaculation ( Hull et al, 1994 ; Sachs, 2000 ; Waldinger and Olivier, 2005 ; Olayo-Lortia et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

A Protocol for the Non-invasive Method of Ultrasound Separation During the Sociosexual Vocal-Non-contact Model in Rats

Bogacki-Rychlik

Wrona

Bialy

2022

Front. Behav. Neurosci.

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Ultrasonic vocalization (USV) is one of the measurable behavioral parameters of sociosexual interactions in rats. To precisely and accurately describe the neurobehavioral properties of USV and the potentially related specific emotional responsiveness of animals, we need to know which animals vocalize and what is their exact behavioral and physiological response. To this end, we modified the non-contact cage [non-contact erection model (NCE)] by adding a modification [vocalization-non-contact erection (VOC-NCE)] that makes it possible to assign emitted ultrasonic signals to a particular animal. Typically, the NCE cage consists of two compartments separated by perforated baffles. A male is placed in one section, and a receptive female is placed in the other section. This makes possible the accurate description of sexual parameters related to the cues controlled by the experimenter. In VOC-NCE, we completely separated the male USV from the female USV by three appropriately perforated baffles and located microphones combined with ultrasonic screening. We recorded emission in both typical bands, the so-called 22- and 50-kHz bands, with various subtypes, thus highlighting the utility of our protocol to investigate the sexual dimorphism of vocalization. Similar to the anticipatory model, we showed that emission can occur without acoustic feedback from concomitants during the VOC-NCE test. Therefore, we propose a relatively simple method for assigning individual vocalization. We discuss its usefulness and limitations in assessing vocal differentiation related to sexual parameters, adaptive changes during conditioning procedures, and further applications.

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“…Both sexual and aggressive behavior in male rats can be described by a "funnel"like pattern of behavior [49][50][51]. By manipulations such as electrical stimulation or lesions in the (ventro)medial hypothalamus, this pattern of behavioral funneling can be interrupted, e.g., electrical stimulation in the VMH in a resident-intruder situation [49] strongly reduces the chance on full aggression, because the stimulation strongly promotes return to phase 1 (scanning and initiation phase).…”

Section: -Ht 1a and 5-ht 1b Receptors In Aggressive And Sexual Behaviormentioning

confidence: 99%

“…Of course, the enhanced 5-HT levels are also not able to stimulate 5-HT 1A heteroreceptors because 5-HT 1A receptor antagonists block these too, but other 5-HT receptors are not blocked and could be instrumental in emerging behaviors. This apparently does not happen: 5-HT 1A receptor antagonists are generally intrinsically silent, i.e., they do not exert intrinsic behavioral effects [51,71,74]. Whether 5-HT 1B autoreceptors plus serotonin transporters completely compensate for the effects of blocking 5-HT 1A receptors on 5-HT release is largely unknown, but seems less likely.…”

Section: Are Effects Of 5-ht 1a -Receptor Agonists and 5-ht 1b -Recep...mentioning

confidence: 99%

Aggression and Sexual Behavior: Overlapping or Distinct Roles of 5-HT_1A and 5-HT_1B Receptors

Olivier¹,

Olivier²

2022

Serotonin and the CNS - New Developments in Pharmacology and Therapeutics

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Distinct brain mechanisms for male aggressive and sexual behavior are present in mammalian species, including man. However, recent evidence suggests a strong connection and even overlap in the central nervous system (CNS) circuitry involved in aggressive and sexual behavior. The serotonergic system in the CNS is strongly involved in male aggressive and sexual behavior. In particular, 5-HT1A and 5-HT1B receptors seem to play a critical role in the modulation of these behaviors. The present chapter focuses on the effects of 5-HT1A- and 5-HT1B-receptor ligands in male rodent aggression and sexual behavior. Results indicate that 5-HT1B-heteroreceptors play a critical role in the modulation of male offensive behavior, although a definite role of 5-HT1A-auto- or heteroreceptors cannot be ruled out. 5-HT1A receptors are clearly involved in male sexual behavior, although it has to be yet unraveled whether 5-HT1A-auto- or heteroreceptors are important. Although several key nodes in the complex circuitry of aggression and sexual behavior are known, in particular in the medial hypothalamus, a clear link or connection to these critical structures and the serotonergic key receptors is yet to be determined. This information is urgently needed to detect and develop new selective anti-aggressive (serenic) and pro-sexual drugs for human applications.

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Antidepressants, Sexual Behavior, and Translational Models for Male Sexual Dysfunction: Development of Animal Models, Pharmacology, and Genetics

Cited by 3 publications

References 220 publications

A new approach to ‘on-demand’ treatment of lifelong premature ejaculation by treatment with a combination of a 5-HT1A receptor antagonist and SSRI in rats

A new approach to ‘on-demand’ treatment of lifelong premature ejaculation by treatment with a combination of a 5-HT1A receptor antagonist and SSRI in rats

A Protocol for the Non-invasive Method of Ultrasound Separation During the Sociosexual Vocal-Non-contact Model in Rats

Aggression and Sexual Behavior: Overlapping or Distinct Roles of 5-HT_1A and 5-HT_1B Receptors

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Antidepressants, Sexual Behavior, and Translational Models for Male Sexual Dysfunction: Development of Animal Models, Pharmacology, and Genetics

Cited by 3 publications

References 220 publications

A new approach to ‘on-demand’ treatment of lifelong premature ejaculation by treatment with a combination of a 5-HT1A receptor antagonist and SSRI in rats

A new approach to ‘on-demand’ treatment of lifelong premature ejaculation by treatment with a combination of a 5-HT1A receptor antagonist and SSRI in rats

A Protocol for the Non-invasive Method of Ultrasound Separation During the Sociosexual Vocal-Non-contact Model in Rats

Aggression and Sexual Behavior: Overlapping or Distinct Roles of 5-HT1A and 5-HT1B Receptors

Contact Info

Product

Resources

About

Aggression and Sexual Behavior: Overlapping or Distinct Roles of 5-HT_1A and 5-HT_1B Receptors