Biology subjects

Luyten, L.

Publications and source records attributed to Luyten, L..

9 recordsLinked to original sources

bioRxiv2025

Pharmacological blockade of opioid receptors in the ventrolateral periaqueductal gray does not affect avoidance acquisition or performance in rats

Avoidance learning involves associating a behavioral response with the omission of an expected threat, but the neural mechanisms that drive this learning remain unclear. Research on fear extinction points to a critical role for opioid receptors in the ventrolateral periaqueductal gray (vlPAG) in computing the aversive prediction error signal that is generated when there is a difference between expected and actual aversive events. Based on these fear extinction findings, we hypothesized that vlPAG opioid signaling might also support the early stages of avoidance learning. To test this, 15 Wistar rats (7 females, 8 males) received intra-vlPAG infusions of either naloxone hydrochloride (n = 7, 2.5 g/0.5 l), a non-selective opioid receptor antagonist, or vehicle (n = 8, 0.5 l), immediately before the first and second session of two-way active avoidance training. No infusions were given before the third session, to examine avoidance performance under continued, drug-free acquisition. For the fourth and final session, drug conditions were reversed to examine the acute effect of naloxone on already established avoidance performance. Our results indicate that unilateral intra-vlPAG naloxone, at the tested dose and timing, did not significantly impair avoidance acquisition, nor its performance. These findings do not support a role for opioid signaling in the vlPAG during the initial learning or expression of two-way active avoidance.

animal behavior and cognition↗

bioRxiv2025

The rewarding properties of safety signals established by a two-way active avoidance task in male rats

Actively avoiding threatening stimuli or situations is an adaptive defensive strategy that minimizes the risk of potential harm. Despite the prominent role avoidance plays in our daily lives, the mechanisms that reinforce avoidance behavior remain incompletely understood. Accumulating evidence implicates the mesolimbic dopamine reward system in the acquisition of avoidance, suggesting that the omission of an aversive event may acquire rewarding properties and function as a positive reinforcer of avoidance behavior. In a series of six experiments (N = 246 male Wistar rats), we examined whether safety signals that coincide with successful avoidance responses in a two-way active avoidance (2WAA) task facilitate avoidance acquisition and acquire reward-like properties, by assessing whether they elicit approach behavior and support the acquisition of a novel instrumental response. Although the presentation of a safety signal accelerated avoidance learning in some experiments, the effect was not consistent. Furthermore, the safety signal neither elicited approach behavior nor supported the acquisition of a novel instrumental response. Together, these findings question whether safety signals in avoidance learning acquire rewarding properties detectable through behavioral measures.

animal behavior and cognition↗

bioRxiv2025

Differential effects of chronic restraint stress on two active avoidance tasks in rats

Although avoidance can serve an adaptive function in daily life, excessive or persistent avoidance can form a debilitating symptom of anxiety-related disorders. The transition from adaptive to maladaptive avoidance remains poorly understood, but stress is a potential contributing factor. We investigated the effects of chronic restraint stress on two active avoidance procedures: two-way active avoidance (2WAA) and platform-mediated avoidance (PMA). Whereas 2WAA entails a low-cost response, avoidance in the PMA task comes with a cost, i.e., no access to food. We hypothesized that chronic restraint stress would hinder avoidance acquisition in the 2WAA task, but increase avoidance acquisition in the PMA task. In two experiments, male and female rats underwent either chronic restraint stress or a control procedure. In Experiment 1, all rats (N = 31) were then trained in a 2WAA acquisition and extinction procedure, in two contexts. Stressed rats showed significantly reduced avoidance acquisition, while extinction was unaffected. In Experiment 2 (N = 32), stressed rats and controls were trained in a PMA acquisition and extinction procedure. Contrary to our hypothesis, we did not find effects on avoidance acquisition, although we found group and sex differences in lever press suppression. All rats gradually extinguished defensive behaviors during extinction. Overall, chronic restraint stress had limited effects on PMA, but significantly impaired avoidance acquisition in the 2WAA task without affecting its extinction. These divergent effects may relate to differences in response cost or differences in safety of the context (i.e., a permanent safe area in PMA, but not in 2WAA). HighlightsO_LIChronic restraint stress impaired acquisition of two-way active avoidance C_LIO_LIChronic restraint stress did not impact acquisition of platform-mediated avoidance C_LIO_LIChronic restraint stress did not impact extinction of avoidance in either task C_LIO_LIMinor sex differences were observed across both tasks C_LI

animal behavior and cognition↗

bioRxiv2024

Increased fear generalization results in reduced generalization of extinction

Generalization of conditioned fear is adaptive for survival. However, overgeneralization of fear from threat cues to loosely similar yet safe stimuli is a hallmark of anxiety-related disorders. Such overgeneralization may impact other fear learning processes. In particular, broad fear generalization might limit the effectiveness of extinction training, which may further maintain anxiety. Here, we examined if increased generalization of conditioned fear might reduce the later generalization of fear extinction. To this end, we compared rats conditioned with moderate-versus high-intensity footshocks, the latter showing stronger generalization of acquired fear than the former. Within each shock intensity group, we then conducted extinction training using the original conditioned stimulus (CS) for half of the animals and a generalization stimulus (GS) for the others. We found stronger preserved responding to the CS after GS extinction in rats that had initially been conditioned using the high-intensity footshock than in rats conditioned using the moderate-intensity footshock, in line with the notion of reduced generalization of extinction from the GS to the CS in the former group. However, we also found indications for weaker retention of GS extinction in rats conditioned with the high-intensity footshock, which may in part or in whole explain the apparent difference in generalization of GS extinction to the CS. Our results may be important to consider in extinction-based exposure therapy, where patients often present with broadly generalized fears and exposure treatment is usually not conducted using the exact cues or situations for which fear was initially acquired. Highlights- We see greater CS-to-GS fear generalization using a strong (vs moderate) US in rats - Paradoxically, we see more preserved CS fear upon GS extinction in the former group - This may reflect an effect on extinction generalization and/or extinction retention - CS extinction reduced GS fear similarly in both groups - Male rats showed higher freezing during acquisition and extinction than females

animal behavior and cognition↗

bioRxiv2024

The impact of systemic blockade of dopamine receptors on the acquisition of two-way active avoidance in rats.

Active threat avoidance is a core aspect of adaptive and maladaptive behavior, yet its underlying mechanisms are not fully understood. Prior studies concluded that pharmacologically blocking dopaminergic receptors (DRs) disrupted avoidance acquisition, but it remains unclear whether such effects on learning persist during a drug-free follow-up test. To assess the involvement of D1R and D2R in avoidance acquisition, we conducted two experiments. In Experiment 1, thirty-six male Wistar rats underwent a single avoidance training session involving 30 tone-shock pairings. Rats could avoid the shock by moving to the opposite compartment of the shuttle box. Twenty minutes before training, rats received either D1R antagonist SCH 23390 (0.05 mg/kg), D2R antagonist sulpiride (20 mg/kg), or vehicle. While sulpiride did not affect avoidance, 0.05 mg/kg SCH 23390 significantly reduced the number of avoidance responses. In a separate test, 0.05 mg/kg SCH 23390 also reduced locomotor activity. In Experiment 2 (N = 24), a lower dose of SCH 23390 (0.025 mg/kg) was administered, and a drug-free avoidance test under continued reinforcement was added 24 hours later to test for sustained effects of D1R blockade on avoidance in the absence of acute drug effects. Although animals avoided less with SCH 23390 in the system, this effect did not persist 24 hours later, suggesting that effects of D1R blockade during avoidance training might reflect an acute disruption of secondary processes involved in the performance of avoidance behavior rather than an actual impairment of avoidance learning.

animal behavior and cognition↗

bioRxiv2024

Generalization and extinction of platform-mediated avoidance in male and female rats

BackgroundUnderstanding the basis of anxiety-related disorders can be advanced by studying the fear learning mechanisms implicated in the transition from adaptive to maladaptive fear. Individuals with anxiety disorders typically exhibit impaired fear extinction, pervasive avoidance, and overgeneralization of fear. While most research has examined deviations in these fear learning characteristics in isolation, their potential interactions remain understudied. Here, we introduce a modification of the platform-mediated avoidance task and use it to chart avoidance, generalization, and extinction using a single procedure in male and female rats. ResultsIn the first experiment, we demonstrated that male rats readily acquire avoidance, show a gradient of generalization in a two-day generalization test, and gradually reduce avoidance and fear responding under extinction. In the second experiment, female rats likewise exhibited successful avoidance learning, showed gradual generalization and extinction of defensive behaviors. Across both experiments, interesting sex differences emerged. The third experiment aimed at corroborating these sex differences but showed that they were subtler than expected from the prior separate experiments. Finally, we present an open-source automated system to facilitate the processing of DeepLabCut and SimBA output and obtain reliable results for scoring avoidance and freezing behavior. ConclusionsThe modified platform-mediated avoidance task can effectively probe avoidance, generalization, and extinction of fear in male and female rats in a single procedure. Our automated behavioral scoring approach offers researchers an efficient and reproducible method to quantify the defensive behaviors of avoidance, freezing and darting in rats.

animal behavior and cognition↗

bioRxiv2023

A history of avoidance does not impact extinction learning in male rats

Pervasive avoidance is one of the central symptoms of all anxiety-related disorders. In treatment, avoidance behaviors are typically discouraged because they are assumed to maintain anxiety. Yet, it is not clear that engaging in avoidance is always detrimental. In this study, we used a platform-mediated avoidance task to investigate the influence of avoidance history on extinction learning in male rats. Our results show that having the opportunity to avoid during fear acquisition training has no marked effect on the extinction of auditory cued fear in a platform-mediated avoidance procedure that constitutes a realistic approach/avoidance conflict in male rats, regardless of whether avoidance was possible during extinction or not. This suggests that imposing a realistic cost on avoidance behavior prevents the adverse effects that avoidance has been claimed to have on extinction, but even then, avoidance does not appear to have clear positive effects on extinction learning nor on retention either.

animal behavior and cognition↗

bioRxiv2022

No evidence that post-training D2R dopaminergic drug administration affects differential fear responding in rats

The neurotransmitter dopamine plays an important role in the processing of emotional memories, and prior research suggests that dopaminergic manipulations immediately after fear learning can affect the retention and generalization of acquired fear. The current study focuses specifically on the role of dopamine D2 receptors (D2Rs) in adult, male Wistar rats. In a series of five experiments, D2R (ant)agonists were injected systemically immediately after differential cued fear conditioning (CS+ followed by shock, CS- without shock). All five experiments involved the administration of the D2R agonist quinpirole at different doses versus saline (n = 12, 16 or 44 rats/group). Additionally, one of the studies administered the D2R antagonist raclopride (n = 12). One day later, freezing during the CS+ and CS- was assessed. We found no indications for an effect of quinpirole or raclopride on fear generalization during this drug-free test. Importantly, and contradicting prior research in mice, the evidence for the absence of an effect of quinpirole (1 mg/kg) on fear generalization was substantial according to Bayesian analyses and was observed in a highly powered experiment (N = 87). We did find acute behavioral effects in line with the literature, for both quinpirole and raclopride in a locomotor activity test.

neuroscience↗

bioRxiv2020

Apparent Reconsolidation Interference Without Generalized Amnesia

Memories remain dynamic after consolidation, and when reactivated, they can be rendered vulnerable to various pharmacological agents that disrupt the later expression of memory (i.e., amnesia). Such drug-induced post-reactivation amnesia has traditionally been studied in AAA experimental designs, where a memory is initially created for a stimulus A (be it a singular cue or a context) and later reactivated and tested through exposure to the exact same stimulus. Using a contextual fear conditioning procedure in rats and midazolam as amnestic agent, we recently demonstrated that drug-induced amnesia can also be obtained when memories are reactivated through exposure to a generalization stimulus (GS, context B) and later tested for that same generalization stimulus (ABB design). However, this amnestic intervention leaves fear expression intact when at test animals are instead presented with the original training stimulus (ABA design) or a novel generalization stimulus (ABC design). The underlying mechanisms of post-reactivation memory malleability and of MDZ-induced amnesia for a generalization context remain largely unknown. Here, we evaluated whether, like typical CS-mediated (or AAA) post-reactivation amnesia, GS-mediated (ABB) post-reactivation amnesia displays key features of a destabilization-based phenomenon. We first show that ABB post-reactivation amnesia is critically dependent on prediction error at the time of memory reactivation and provide evidence for its temporally graded nature. In line with the known role of GluN2B-NMDA receptor activation in memory destabilization, we further demonstrate that pre-reactivation administration of ifenprodil, a selective antagonist of GluN2B-NMDA receptors, prevents MDZ-induced ABB amnesia. In sum, our data reveal that ABB MDZ-induced post-reactivation amnesia exhibits the hallmark features of a destabilization-dependent phenomenon. Implication of our findings for a reconsolidation-based account of post-reactivation amnesia are discussed.

neuroscience↗