Biology subjects

Heijkoop, R.

Publications and source records attributed to Heijkoop, R..

11 recordsLinked to original sources

bioRxiv2026

Specialized and experience-dependent neural dynamics in the medial amygdala and bed nucleus of stria terminalis upon social and sexual olfactory and tactile cues

The medial amygdala (MeApd) and bed nucleus of the stria terminalis (BNST) are central components of the social behavior network. However, their real-time activity during social and sexual interactions, and their respective contributions to processing olfactory and tactile cues, remain unclear. Here, we used simultaneous dual site fiber photometry to record GCaMP6s signals from the MeApd and BNST in freely behaving male rats during social interaction, copulation, sexual exhaustion, and vaginal occlusion tests. Introduction of a conspecific increased activity in both regions, but the response profiles differed by social context and experience. The MeApd responded robustly to male and female conspecifics, with larger responses to males, whereas BNST activity increased reliably upon female introduction only after sexual experience. During olfactory investigation of a male conspecific, MeApd activity differentiated sniffing of anterior and posterior body regions, while BNST activity showed no comparable spatial selectivity. Neither region showed robust event-aligned responses during sniffing of receptive females. Tactile stimulation during copulation elicited strong calcium responses in both regions. Mounts, intromissions, and ejaculations each triggered significant activity, with ejaculation producing the largest responses. MeApd responses differentiated ejaculation from mounting in sexually naive animals, whereas distinctions in BNST responses emerged primarily after sexual experience. Moreover, responses to intromissions and ejaculations persisted during the final ejaculatory series preceding sexual exhaustion, while responses to mounts were eliminated when vaginal penetration was prevented. Together, these findings identify specialized yet parallel activity dynamics within the MeApd-BNST network. MeApd activity preferentially tracks socially relevant olfactory investigation and the intensity of copulatory sensory feedback, whereas BNST recruitment during sexual behavior is more strongly shaped by sexual experience.

neuroscience↗

bioRxiv2026

Behavioral dynamics of different stages of sexual motivation in male and female rats

Sexual motivation is a complex concept involving both the initial drive to begin mating and the motivation to sustain copulation. Disruptions in sexual motivation are often observed in psychiatric disorders. This study proposes that sexual motivation can be divided into two distinct components: sexual incentive motivation and the drive to sustain copulation. To investigate this, we utilized the Motivation to Continue Copulation (MCC) test, which measures effort (nose pokes) to gain access to a sexual reward, and compared it with the Sexual Incentive Motivation (SIM) test and standard copulation tests. Male and female rats were trained on a fixed ratio (FR) 1 schedule using cheese rewards before transitioning to sexual rewards. After six FR1 sessions, the effort required increased to FR5 and progressive ratio (PR) schedules. Results revealed that sexual incentive motivation, measured by the SIM test, was higher in males after sexual experience, while females maintained consistent levels. In the MCC test, both males and females exhibited increased motivation to continue copulation with experience, but the motivation declined in the 2nd ejaculatory series. These findings demonstrate that sexual motivation comprises distinct components. The MCC test effectively measures the drive to sustain copulation, while the SIM test assesses incentive motivation. This distinction is crucial for advancing behavioral neuroscience and understanding sexual dysfunction in psychiatric conditions.

neuroscience↗

bioRxiv2025

Perinatal fluoxetine exposure increases male rat sexual behavior

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to pregnant women due to their efficacy and safety profile, leading to potential exposure of the developing fetus and infant. Serotonin, which acts as a neurotransmitter in adults and is crucial for regulating male sexual behavior, also serves as a neurotrophic factor during early brain development. Yet, the long-term consequences of perinatal SSRI exposure on adult sexual functioning remain poorly understood. This study investigates the long-term effects of perinatal SSRI exposure on the sexual behavior of adult male rats in a seminatural environment. During pregnancy and lactating, mother rats were administered either fluoxetine (FLX, 10 mg/kg) or a control solution (CTR, 1% Methylcellulose) daily via oral gavage. Upon reaching adulthood, male offspring were assessed for sexual performance in a semi-natural setting, where they lived in mixed-sex groups for eight days. Comprehensive observations of sexual, social, and conflict behaviors were scoring from the first to the last copulatory behavior during the period in which female rats were sexually receptive. Our findings reveal that perinatal FLX exposure significantly increases sexual behavior in adult male rats, as evidenced by a higher total number of copulatory behaviors. This suggests that elevated serotonin levels during early development have enduring consequences for male rat sexual behavior in adulthood, potentially enhancing reproductive strategies and success in naturalistic environments.

neuroscience↗

bioRxiv2024

Behavioral and neural alterations of the ventral tegmental area by Cafeteria diet exposure in rats

The brain reward system is essential for regulating appetitive and consummatory behaviors in response to various incentive stimuli. Junk food, characterized by its high palatability, is particularly associated with the potential for excessive consumption. While prior studies indicate that excessive junk food intake can impact reward circuitry, the precise mechanisms underlying these effects remain elusive. Furthermore, it is unclear whether the functionality of this neural system is similarly altered in response to other natural rewards. In this study, we used fiber photometry combined with a behavioral reward test to investigate the effects of six weeks of excessive cafeteria (CAF) diet consumption on ventral tegmental area (VTA) neural activity and behavioral responses to food and sexual rewards in female rats. Our findings demonstrate that prolonged exposure to a CAF diet reduced the exploration and consumption of food rewards. These behavioral changes were accompanied by attenuated neural activity in the VTA. Similarly, reductions in VTA activity were observed in response to a sexual partner, although no significant behavioral differences were detected during sexual interactions. Moreover, a two-week reversal diet of standard chow proved insufficient to restore VTA neural activity in CAF-exposed animals, which continued to exhibit decreased VTA responses to both food rewards and sexual partners. Our results suggest that prolonged junk food exposure induces desensitization of the VTA, resulting in reduced responsiveness to natural rewards. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/618156v3_ufig1.gif" ALT="Figure 1"> View larger version (79K): org.highwire.dtl.DTLVardef@63c782org.highwire.dtl.DTLVardef@bf2e28org.highwire.dtl.DTLVardef@16f7ad8org.highwire.dtl.DTLVardef@1ea1235_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

The temporal copulatory patterns of female rat sexual behavior

Female sexual behavior is a naturally rewarding activity that plays an important role in reproduction and species survival. For female rats, regulating the timing of sexual interactions is essential for optimizing mating satisfaction and enhancing the physiological conditions needed for successful fertilization. So far, traditional research on female sexual behavior has relied on a limited set of behavioral parameters, which has certain shortcomings. To address this, our study aimed to develop a more detailed behavioral framework for assessing temporal copulatory patterns in female rats. We compared fully receptive females and less-receptive females, while also investigating the effects of (R)-(+)-8-OH-DPAT, a 5-HT1A receptor agonist known for its inhibitory impact on female sexual behavior. Additionally, we examined how sexual experience and pacing conditions influence these copulatory patterns. Our results revealed that female rats engage in structured patterns of sexual bouts and time-outs, with higher receptivity leading to more sexual bouts and shorter time-outs. This suggests that sexual bouts can be viewed as an indicator of copulatory intensity, while time-outs reflect motivation to continue mating. Sexual experience did not enhance sexual performance but did result in females receiving more copulatory events from males. Lastly, we found that the conditions under which mating occurs (paced vs. non-paced) may not significantly impact copulatory behavior in fully-receptive females but could be more relevant for less-receptive females. Despite this, paced mating conditions remain preferable for studying female sexual behavior.

animal behavior and cognition↗

bioRxiv2023

Changes in reward-induced neural activity upon Cafeteria Diet consumption

Excessive consumption of highly palatable foods rich in sugar and fat, often referred to as "junk" or "fast" foods, plays a central role in the development of obesity. The highly palatable characteristics of these foods activate hedonic and motivational mechanisms to promote food-seeking behavior and overeating, which is largely regulated by the brain reward system. Excessive junk food consumption can alter the functioning of this reward system, but exact mechanisms of these changes are still largely unknown. This study investigated whether long-term junk food consumption, in the form of Cafeteria (CAF) diet, can alter the reward system in adult, female Long-Evans rats, and whether different regimes of CAF diet influence the extent of these changes. To this end, rats were exposed to a 6-week diet with either standard chow, or ad libitum daily access to CAF diet, 30% restricted but daily access to CAF diet, or one-day-a-week (intermittent) ad libitum access to CAF diet, after which c-Fos expression in the Nucleus Accumbens (NAc), Prefrontal Cortex (PFC), and Ventral Tegmental Area (VTA) following consumption of a CAF reward of choice was examined. We found that all CAF diet regimes decreased c-Fos expression in the NAc-shell when presented with a CAF reward, while no changes in c-Fos expression upon the different diet regimes were found in the PFC, and possibly the VTA. Our data suggests that long-term junk food exposure can affect the brain reward system, resulting in an attenuated activity of the NAc-shell.

neuroscience↗

bioRxiv2023

CaMKIIa+ neurons in the bed nucleus of the stria terminalis area modulate pace of natural reward seeking depending on internal state

This study aims to investigate the underlying neurobiological mechanisms that regulate natural reward seeking behaviors, specifically in the context of sexual behavior and sucrose self-administration. The role of CaMKIIa+ neurons in the bed nucleus of the stria terminalis (BNST) was explored using chemogenetic silencing and -stimulation. Additionally, the study examined how these effects interacted with the internal state of the animals. Through detailed behavioral analysis, it was demonstrated that CaMKIIa+ neurons in the BNST play a significant role in the regulation of both sexual behavior and sucrose self-administration. Although the behavioral outcome measures differed between the two behaviors, the regulatory role of the CaMKIIa+ neurons in the BNST was found to converge on the modulation of the pacing of engagement in these behaviors in male rats. Moreover, our study confirmed that the internal physiological state of the animal affects how the BNST modulates these behaviors. These findings suggest that different types of natural rewards may recruit a similar brain circuitry to regulate the display of motivated behaviors. Overall, this research provides valuable insights into the neural mechanisms underlying natural reward seeking and sheds light on the interconnected nature of reward-related behaviors in male rats. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/558107v2_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1000720org.highwire.dtl.DTLVardef@d3ea4aorg.highwire.dtl.DTLVardef@bacac1org.highwire.dtl.DTLVardef@1557163_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Effects of Perinatal Fluoxetine Exposure on Novelty-induced Social and Non-Social Investigation Behaviors in a Seminatural Environment

Selective serotonin reuptake inhibitors (SSRIs) are increasingly prescribed as medication for various affective disorders during pregnancy. SSRIs cross the placenta and affect serotonergic neurotransmission in the fetus, but the neurobehavioral consequences for the offspring remain largely unclear. Recent rodent research has linked perinatal SSRI exposure to alterations in both social and non-social aspects of behavior. However, this research has mainly focused on behavior within simplified environments. The current study investigates the effects of perinatal SSRI exposure on social and non-social investigation behaviors of adult rat offspring upon introduction to a novel seminatural environment with unknown conspecifics. During the perinatal period (gestational day 1 until postnatal day 21), rat dams received daily treatment with either an SSRI (fluoxetine, 10 mg/kg) or vehicle. Adult male and female offspring were observed within the first hour after introduction to a seminatural environment. The results showed that perinatal fluoxetine exposure altered aspects of non-social investigation behaviors, while not altering social investigation behaviors. More specifically both fluoxetine exposed males and females spent more total time on locomotor activity than controls. Furthermore, fluoxetine exposed females spent less time exploring objects and specific elements in the environment. The data suggest that perinatal exposure to SSRIs leads to a quicker, less detailed investigation strategy in novel environments, and that the alteration is mostly pronounced in females.

animal behavior and cognition↗

bioRxiv2021

Silencing and stimulating the medial amygdala impairs ejaculation but not sexual incentive motivation in male rats

The medial amygdala (MeA) is a sexually dimorphic brain region that integrates sensory information and hormonal signaling, and is involved in the regulation of social behaviors. Lesion studies have shown a role for the MeA in copulation, most prominently in the promotion of ejaculation. The role of the MeA in sexual motivation, but also in temporal patterning of copulation, has not been extensively studied in rats. Here, we investigated the effect of chemogenetic inhibition and stimulation of the MeA on sexual incentive motivation and copulation in sexually experienced male rats. AAV5-CaMKIIa viral vectors coding for Gi, Gq, or no DREADDs (sham) were bilaterally infused into the MeA. Rats were assessed in the sexual incentive motivation test and copulation test upon systemic CNO or vehicle administration. We report that MeA stimulation and inhibition did not affect sexual incentive motivation. Moreover, both stimulation and inhibition of the MeA decreased the number of ejaculations in a 30 minute copulation test and increased ejaculation latency and the number of mounts and intromissions preceding ejaculation, while leaving the temporal pattern of copulation intact. These results indicate that the MeA may be involved in the processing of sensory feedback required to reach ejaculation threshold. The convergence of the behavioral effects of stimulating as well as inhibiting the MeA may reflect opposing behavioral control of specific neuronal populations within the MeA.

neuroscience↗

bioRxiv2020

Female rat sexual behavior is unaffected by perinatal fluoxetine exposure

Serotonin plays an important role in adult female sexual behavior, however little is known about the influence of serotonin during early development on sexual functioning in adulthood. During early development, serotonin acts as neurotrophic factor, while it functions as a modulatory neurotransmitter in adulthood. The occurrence of serotonin release, could thus have different effects on behavioral outcomes, depending on the developmental period in which serotonin is released. Because serotonin is involved in the development of the HPG axis which is required for puberty establishment, serotonin could also alter expression patterns of for instance the estrogen receptor (ER). The aim of our study was to investigate the effects of increased serotonin levels during early development on adult female rat sexual behavior during the full behavioral estrus in a seminatural environment. To do so, rats were perinatally exposed with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (10 mg/kg FLX) and sexual performance was tested during adulthood. All facets of female sexual behavior between the first and last lordosis (behavioral estrus), and within each copulation bout of the behavioral estrus were analyzed. Besides the length and onset of the behavioral estrus and the sexual behaviors patterns, other social and conflict behavior were also investigated. In addition, we studied the effects of perinatal FLX exposure on ER expression patterns in the medial preoptic nucleus, ventromedial nucleus of the hypothalamus, medial amygdala, bed nucleus of the stria terminalis, and the dorsal raphe nucleus. The results showed that perinatal fluoxetine exposure has no effect on adult female sexual behavior. The behavioral estrus of FLX-females had the same length and pattern as CTR-females. In addition, FLX- and CTR-females showed the same amount of paracopulatory behavior and lordosis, both during the full behavioral estrus and the "most active bout". Furthermore, no differences were found in the display of social and conflict behaviors, nor in ER expression patterns in the brain. We conclude that increases in serotonin levels during early development do not have long-term consequences for female sexual behavior in adulthood.

animal behavior and cognition↗

bioRxiv2019

Third-party prosocial behavior in adult female rats is impaired after perinatal fluoxetine exposure

SSRIs are commonly used to treat pregnant women with depression. However, SSRIs can cross the placenta and affect the development of the fetus. The effects of perinatal SSRI exposure, and especially the effects on social behavior, are still incompletely documented. This study first aims to investigate whether rats show prosocial behavior in the form of consolation behavior. Secondly, it aims to investigate whether perinatal SSRI exposure affects this prosocial behavior. At last, we investigate whether the behavior changed after the rats had been exposed to an additional white-noise stressor. Rat dams received 10 mg/kg/d fluoxetine (FLX) or vehicle (CTR) via oral gavage from gestational day 1 until postnatal day 21. At adulthood, the rat offspring were housed in four cohorts of 4 females and 4 males in a seminatural environment. As prosocial behaviors are more prominent after stressful situations, we investigated the behavioral response of rats immediately after natural aggressive encounters (fights). Additionally, we studied whether a stressful white-noise exposure would alter this response to the aggressive encounters. Our study indicates that CTR-female rats are able to show third party prosocial behavior in response to witnessing aggressive encounters between conspecifics in a seminatural environment. In addition, we showed that perinatal FLX exposure impairs the display of prosocial behavior in female rats. Moreover, we found no signs of prosocial behavior in CTR- and FLX-males after natural aggressive encounters. After white-noise exposure the effects in third party prosocial behavior of CTR-females ceased to exist. We conclude that female rats are able to show prosocial behavior, possibly in the form of consolation behavior. In addition, the negative effects of perinatal fluoxetine exposure on prosocial behavior could provide additional evidence that SSRI treatment during pregnancy could contribute to the risk for social impairments in the offspring.

animal behavior and cognition↗