Fear‐Potentiated Startle and Light‐Enhanced Startle Models in Drug Discovery

Groenink, Lucianne; Bijlsma, Elisabeth Y.; Olivier, Berend

doi:10.1002/0471141755.ph0548s41

Cited by 6 publications

(7 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the emergence of impaired social interaction following PYY treatment is in agreement with the effects of the Y2 receptor antagonist BIIE0246 that has been shown to increase active contacts in a rat social interaction test (Morales-Medina et al, 2012a). The expressions of startle responses (and consequently the amount of PPI) and social interaction are, to some degree, influenced by innate and/or conditioned forms of anxiety (Brodkin, 2007;Groenink et al, 2008). Here, we did not reveal any significant effects of PYY 3-36 on anxiety-related behavior in the elevated plus maze test.…”

Section: Discussionsupporting

confidence: 74%

Administration of the Y2 Receptor Agonist PYY3-36 in Mice Induces Multiple Behavioral Changes Relevant to Schizophrenia

Stadlbauer

Langhans

Meyer

2013

Neuropsychopharmacol

View full text Add to dashboard Cite

Functional changes in neuropeptide Y (NPY) signaling at the Y2 receptor subtype have been widely implicated in stress-related neuropsychiatric illnesses such as depression and anxiety disorders. Altered Y2 receptor signaling may also play a role in the precipitation of behavioral and cognitive symptoms associated with schizophrenia. To seek preclinical evidence for this possibility, we explored the functional consequences of treatment with the selective Y2 receptor agonist PYY 3-36 using translational tests for the assessment of schizophrenia-relevant behavioral and cognitive deficits in mice. We found that acute systemic administration of PYY 3-36 at a low dose (1 mg/100 g body weight) or high dose (20 mg/100 g body weight) profoundly impaired social interaction without affecting innate anxiety. PYY 3-36 treatment at the high dose further led to a disruption of sensorimotor gating in the form of prepulse inhibition deficiency. This effect was fully antagonized by acute treatment with the preferential dopamine D2 receptor antagonist haloperidol, but not with clozapine. In addition, both doses of PYY 3-36 impaired selective associative learning in the latent inhibition paradigm and spatial working memory in a matching-to-position water maze test. The wide range of abnormalities induced by PYY suggests that signaling at the Y2 subtype of NPY receptors is critical for a number of behavioral and cognitive functions, some of which are highly relevant to schizophrenia and related psychotic disorders. At least some of the behavioral deficits induced by augmentation of Y2 receptor signaling may involve increased dopaminergic activity.

show abstract

Section: Discussionsupporting

confidence: 74%

Administration of the Y2 Receptor Agonist PYY3-36 in Mice Induces Multiple Behavioral Changes Relevant to Schizophrenia

Stadlbauer

Langhans

Meyer

2013

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…During the test session, acoustic stimuli are presented in the absence or presence of the conditioned stimulus. The magnitude of the startle response elicited in the presence of the conditioned stimulus (cued trial, C ) relative to the response in absence of the conditioned stimulus (non-cued trial, C , white dotted bar) is taken as an index of cued-conditioned fear and can be used to measure the anxiolytic effect of the administered drug (Groenink et al 2008 ). The magnitude of the startle response in the absence of the conditioned stimulus (non-cued trial, C , white bar) is considered the baseline response and is used to control for potential adverse drug effects, such as sedation and motor effects.…”

Section: Introductionmentioning

confidence: 99%

“…In humans, both cued-conditioned and sustained contextual anxiety states can well be discriminated and measured within the same fear potentiation startle test (Baas et al 2004 ). In a standard fear-potentiated startle test in animals, contextual fear cannot readily be assessed, which could be seen as a limitation of the test (Groenink et al 2008 ).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological modulation of conditioned fear in the fear-potentiated startle test: a systematic review and meta-analysis of animal studies

et al. 2023

Self Cite

View full text Add to dashboard Cite

Rationale and objectives Fear conditioning is an important aspect in the pathophysiology of anxiety disorders. The fear-potentiated startle test is based on classical fear conditioning and over the years, a broad range of drugs have been tested in this test. Synthesis of the available data may further our understanding of the neurotransmitter systems that are involved in the expression of conditioned fear. Methods Following a comprehensive search in Medline and Embase, we included 68 research articles that reported on 103 drugs, covering 56 different drug classes. The systematic review was limited to studies using acute, systemic drug administration in naive animals. Results Qualitative data synthesis showed that most clinically active anxiolytics, but not serotonin-reuptake inhibitors, reduced cued fear. Anxiogenic drugs increased fear potentiation in 35% of the experiments, reduced fear potentiation in 29% of the experiments, and were without effect in 29% of the experiments. Meta-analyses could be performed for five drug classes and showed that benzodiazepines, buspirone, 5-HT1A agonists, 5-HT1A antagonists, and mGluR2,3 agonists reduced cued conditioned fear. The non-cued baseline startle response, which may reflect contextual anxiety, was only significantly reduced by benzodiazepines and 5-HT1A antagonists. No associations were found between drug effects and methodological characteristics, except for strain. Conclusions The fear-potentiated startle test appears to have moderate to high predictive validity and may serve as a valuable tool for the development of novel anxiolytics. Given the limited available data, the generally low study quality and high heterogeneity additional studies are warranted to corroborate the findings of this review.

show abstract

“…Conditioned fear-potentiated startle (FPS) is one model of cued fear-related behavior used to study associative learning processes that support the development and maintenance of PTSD symptomatology [34]. The FPS model has face, construct, and predictive validity [35,36,37,38], and therefore provides a valid and relevant methodology for identifying treatments for PTSD. We have done extensive work repeatedly demonstrating that HAP1 and HAP2 mouse lines show greater FPS than LAP1 and LAP2 lines [39,40,41].…”

Section: Introductionmentioning

confidence: 99%

Endocannabinoids and Fear-Related Behavior in Mice Selectively Bred for High or Low Alcohol Preference

2019

View full text Add to dashboard Cite

Alcohol use disorders (AUDs) have a high incidence of co-morbidity with stress-related psychopathologies, such as post-traumatic stress disorder (PTSD). Genetic and pharmacological studies support a prominent role for the endocannabinoid system (ECS) in modulating stress-related behaviors relevant to AUDs and PTSD. Mouse lines selectively bred for high (HAP) and low (LAP) alcohol preference show reproducible differences in fear-potentiated startle (FPS), a model for PTSD-related behavior. The first experiment in this study assessed levels of the endocannabinoids, anandamide (AEA) and sn-2 arachidonylglycerol (2-AG), in the prefrontal cortex (PFC), amygdala (AMG), and hippocampus (HIP) of male and female HAP1 and LAP1 mice following the expression of FPS to determine whether ECS responses to conditioned-fear stress (FPS) were correlated with genetic propensity toward high or low alcohol preference. The second experiment examined effects of a cannabinoid receptor type 1 agonist (CP55940) and antagonist (rimonabant) on the expression of FPS in HAP1 and LAP1 male and female mice. The estrous cycle of females was monitored throughout the experiments to determine if the expression of FPS differed by stage of the cycle. FPS was greater in male and female HAP1 than LAP1 mice, as previously reported. In both experiments, LAP1 females in diestrus displayed greater FPS than LAP1 females in metestrus and estrus. In the AMG and HIP, AEA levels were greater in male fear-conditioned HAP1 mice than LAP1 mice. There were no line or sex differences in effects of CP55940 or rimonabant on the expression of FPS. However, surprisingly, evidence for anxiogenic effects of prior treatment with CP55940 were seen in all mice during the third drug-free FPS test. These findings suggest that genetic differences in ECS function in response to fear-conditioning stress may underlie differences in FPS expression in HAP1 and LAP1 selected lines.

show abstract

Fear‐Potentiated Startle and Light‐Enhanced Startle Models in Drug Discovery

Cited by 6 publications

References 26 publications

Administration of the Y2 Receptor Agonist PYY3-36 in Mice Induces Multiple Behavioral Changes Relevant to Schizophrenia

Administration of the Y2 Receptor Agonist PYY3-36 in Mice Induces Multiple Behavioral Changes Relevant to Schizophrenia

Pharmacological modulation of conditioned fear in the fear-potentiated startle test: a systematic review and meta-analysis of animal studies

Endocannabinoids and Fear-Related Behavior in Mice Selectively Bred for High or Low Alcohol Preference

Contact Info

Product

Resources

About