Major depression is frequently associated with sexual dysfunctions. Most antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), induce additional sexual side effects and, although effective antidepressants, deteriorate sexual symptoms, which are the main reason that patients stop antidepressant treatment. Many strategies have been used to circumvent the additional sexual side effects, but results are rather disappointing. Recently, new antidepressants have been introduced, vilazodone and vortioxetine, which seem to lack sexual side effects in the early registration trials. Much research with large numbers of depressed patients and adequate methodological tools still has to confirm in daily use the absence of sexual side effects of new antidepressants. Animal models that in an early phase of drug development may predict putative sexual side effects of new antidepressants are extremely useful and could speed up development of new antidepressants. A rat model of sexual behavior is described that has a very high predictive validity for sexual side effects in man. Several characteristics of present antidepressants with regard to sexual dysfunctions are also present in the rat model and establish its validity. The animal model can also be used in the search for new psychotropics without sexual side effects or for drugs with sexual stimulating activity.
Part of the book: Sexual Dysfunction
Maternal vulnerability to adversity has long-term impact on the developing child. About 20% of the pregnant women suffer from affective disorders. Fetal exposure to maternal adversity may lead to detrimental consequences later in life. Maternal affective disorders are increasingly treated with antidepressants, especially selective serotonin reuptake inhibitors (SSRIs). However, the long-term consequences for the offspring after exposure to this medication are unclear. The interplay between maternal adversity and SSRI treatment has been under investigation and here we discuss how maternal adversity and SSRIs are able to shape offspring development. Specifically, we will discuss animal models addressing behavioral outcomes to understand how the prenatal environment influences the health of the developing child across the life span.
Part of the book: Antidepressants
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.
Part of the book: Serotonin and the CNS
The olfactory bulbectomized (OBX) rat is extensively used as an animal model to detect putative antidepressant drugs. The model has some unusual characteristics, as it detects antidepressant activity of drugs only after medium to long-term administration, thereby reflecting the human situation, as antidepressants do not work acutely but only after long-term administration. The slow onset of action of antidepressants is a major drawback of current antidepressants and the availability of an animal depression model that potentially reveals rapid onset of antidepressant activity might be a great asset. Although an animal model of depression ideally should reflect correlates of human depression, several ‘surrogate’ parameters, like ‘hyperactivity’, reflect astonishingly well the ‘antidepressant’ profile of antidepressants in human depression. Using a new environment (open field) and a home cage to measure activity, imipramine, a classic tricyclic antidepressant, reduced hyperactivity in OBX rats, both in home cage and open field. Telemetrically measured, OBX-induced hyperactivity was already found after a couple of days and indicated that the OBX model is able to detect early (days) effects of (classic) antidepressants. Although imipramine treatment for 3, 7 and 14 days reduced OBX-induced hyperactivity, daily treatment with imipramine for 14 days, but not for 3 or 7 days, reduced hyperactivity (both in home cage and open field) of OBX rats up to 6 weeks after cessation of treatment, indicating neuroplastic changes in the brain. The attractiveness of the OBX model for detection of antidepressants lies in the resemblance to the human situation (onset of action). Moreover, the model suggests that long-term antidepressant treatment (in rats at least 14 days) leads to long-term behavioral changes that far outlast the presence of the antidepressant in the body. Whether this aspect contributes to efficient antidepressant effects needs further investigation.
Part of the book: COVID-19 Pandemic, Mental Health and Neuroscience