Biology subjects

Vervliet, B.

Publications and source records attributed to Vervliet, B..

8 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

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↗

bioRxiv2023

Overnight fasting facilitates safety learning by changing the neurophysiological response to relief from threat omission

Excessive avoidance and slow extinction of fear are hallmarks of anxiety disorders. We have previously found that overnight fasting diminishes excessive avoidance and speeds up fear extinction by decreasing subjective relief during threat omissions. Since relief tracks the reward prediction error signal that governs safety learning, we hypothesized that these effects of fasting might be linked to a decreased activation in brain regions related to reward prediction error processing. Hence, we replicated our previous study in a 3T-MRI scanner. Overnight fasting increased effective avoidance and sped up fear extinction learning. During extinction, the fasting group showed lower activations in the ventromedial prefrontal cortex and nucleus accumbens in response to threat omissions signaled by a safe cue. Nucleus accumbens activations were modulated by relief in the control group. This study provides support for overnight fasting as an adjunct to treatments for anxiety, but the effects should be investigated in anxious patients.

neuroscience↗

bioRxiv2023

Omissions of Threat Trigger Subjective Relief and Reward Prediction Error Like Signaling in the Human Reward System

The unexpected absence of danger constitutes a pleasurable event that is critical for the learning of safety. Accumulating evidence points to similarities between the processing of absent threat and the well-established reward prediction error (PE). However, clear-cut evidence for this analogy in humans is scarce. In line with recent animal data, we showed that the unexpected omission of (painful) electrical stimulation triggers activations within key regions of the reward and salience pathways and that these activations correlate with the pleasantness of the reported relief. Furthermore, by parametrically violating participants probability and intensity related expectations of the upcoming stimulation, we showed for the first time in humans that omission-related activations in the VTA/SN were stronger following omissions of more probable and intense stimulations, like a positive reward PE signal. Together, our findings provide additional support for an overlap in the neural processing of absent danger and rewards in humans.

neuroscience↗

bioRxiv2021

Cortico-striatal activity characterizes human safety learning via Pavlovian conditioned inhibition

Safety learning generates associative links between neutral stimuli and the absence of threat, promoting the inhibition of fear and security-seeking behaviours. Precisely how safety learning is mediated at the level of underlying brain systems, particularly in humans, remains unclear. Here, we integrated a novel Pavlovian conditioned inhibition task with ultra-high field (UHF) fMRI to examine the neural basis of inhibitory safety learning in 49 healthy participants. In our task, participants were conditioned to two safety signals: a conditioned inhibitor that predicted threat-omission when paired with a known threat signal (A+/AX-), and a standard safety signal that generally predicted threat-omission (BC-). Both safety signals evoked equivalent autonomic and subjective learning responses but diverged strongly in terms of underlying brain activation. The conditioned inhibitor was characterized by more prominent activation of the dorsal striatum, anterior insular and dorsolateral prefrontal cortex compared to the standard safety signal, whereas the latter evoked greater activation of the ventromedial prefrontal cortex, posterior cingulate and hippocampus, among other regions. Further analyses of the conditioned inhibitor indicated that its initial learning was characterized by consistent engagement of dorsal striatal, midbrain, thalamic, premotor, and prefrontal subregions. These findings suggest that safety learning via conditioned inhibition involves a distributed cortico-striatal circuitry, separable from broader cortical regions involved with processing standard safety signals (e.g., CS-). This cortico-striatal system could represent a novel neural substrate of safety learning, underlying the initial generation of stimulus-safety associations, distinct from wider cortical correlates of safety processing, which facilitate the behavioral outcomes of learning. Significance statementIdentifying safety is critical for maintaining adaptive levels of anxiety, but the neural mechanisms of human safety learning remain unclear. Using ultra-high field fMRI, we compared learning-related brain activity for a conditioned inhibitor, which actively predicted threat-omission, and a standard safety signal (CS-), which was passively unpaired with threat. The inhibitor engaged an extended circuitry primarily featuring the dorsal striatum, along with thalamic, midbrain, and premotor/prefrontal cortex regions. The CS-exclusively involved cortical safety-related regions observed in basic safety conditioning, such as the vmPFC. These findings extend current models to include learning-specific mechanisms for encoding stimulus-safety associations, which might be distinguished from expression-related cortical mechanisms. These insights may suggest novel avenues for targeting dysfunctional safety learning in psychopathology.

neuroscience↗

bioRxiv2021

Scopolamine blocks context-dependent reinstatement of fear responses in rats

Return of fear poses a problem for extinction-based therapies of clinical anxiety. Experimental research has discovered several pathways to return of fear, one of which is known as reinstatement. Here, we evaluated in rats the potential of scopolamine, a non-selective muscarinic receptor antagonist that is also safe for use in humans, to prevent the reinstatement of extinguished fear. We conducted three experiments with a total sample of 96 female rats. All rats went through a fear acquisition session (tone-shock pairings, CS-US), followed by two extinction sessions (CS only) and a post-extinction fear memory test. Twenty-four hours later, rats were placed in the same or a different context from extinction and received two unsignaled foot shock (US) presentations. On the following day, CS-evoked freezing returned when the reinstating USs had occurred in the same context compared to a different context (context-dependent reinstatement, Experiment 1). Systemic administration of scopolamine before or after the reinstating USs blocked the return of CS-evoked freezing on the following day (Experiments 2 and 3). Our findings suggest that administering scopolamine around the time of an aversive experience could prevent relapse of extinguished fears in humans.

neuroscience↗