Biology subjects

Lopez-Moraga, A.

Publications and source records attributed to Lopez-Moraga, A..

5 recordsLinked to original sources

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↗

bioRxiv2025

Separable Dorsal Raphe Dopamine Projections mediate the Facets of Loneliness-like state

Affiliative social connections facilitate well-being and survival in numerous species. Engaging in social interactions requires positive or negative motivational drive, elicited through coordinated activity across neural circuits. However, the identity, interconnectivity, and functional encoding of social information within these circuits remains poorly understood. Here, we focus on downstream projections of dorsal raphe nucleus (DRN) dopamine neurons (DRNDAT), which we previously implicated in social motivation alongside an aversive affective state. We show that three prominent DRNDAT projections - to the bed nucleus of the stria terminalis (BNST), central amygdala (CeA), and posterior basolateral amygdala (BLP) - play separable roles in behavior, despite substantial collateralization. Photoactivation of the DRNDAT-CeA projection promoted social behavior and photostimulation of the DRNDAT-BNST projection promoted exploratory behavior, while the DRNDAT-BLP projection supported place avoidance, suggesting a negative affective state. Downstream regions showed diverse receptor expression, poising DRNDAT neurons to act through dopamine, neuropeptide, and glutamate transmission. Furthermore, we show ex vivo that the effect of DRNDAT photostimulation on downstream neuron excitability depended on region and baseline cell properties, resulting in excitatory responses in BNST cells and diverse responses in CeA and BLP. Finally, in vivo microendoscopic cellular-resolution recordings in the CeA with DRNDAT photostimulation revealed a correlation between social behavior and neurons excited by social stimuli- suggesting that increased dopamine tone may recruit different CeA neurons to social ensembles. Collectively, these circuit features may facilitate a coordinated, but flexible, response in the presence of social stimuli that can be flexibly guided based on the internal social homeostatic need state of the individual.

neuroscience↗

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↗

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↗