Disturbed social behavior and motivation in rats selectively bred for deficient sensorimotor gating

Dieckmann, Marco; Freudenberg, Florian; Klein, Steffen; Koch, Michael; Schwabe, Kerstin

doi:10.1016/j.schres.2007.08.007

Cited by 28 publications

(12 citation statements)

References 15 publications

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“…Deficits in social behavior and motivation have also been reported in the low-PPI rats [60], thus even supporting their validity as a model for some negative symptoms of schizophrenia. Moreover, haloperidol, but not clozapine, has been found to reverse the PPI deficits of that rat line [61].…”

Section: Selective Breeding Of Reduced Sensorimotor Gating: the Low-amentioning

confidence: 66%

Genetic Rat Models of Schizophrenia-Relevant Symptoms

Río¹,

Oliveras²,

Cañete³

et al. 2014

WJNS

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It is recognized that developing valid animal models is essential for the research on the neurobiological mechanisms of (and treatments for) psychiatric disorders, even when these are as complex as schizophrenia. To be considered a valid analogue of the disorder, a given model should present good face validity (i.e. similarity of symptoms), good predictive validity (i.e. similarity of treatment effects and potential for discovering novel treatments) and enough construct validity (i.e. the model should help discover neurobiological mechanisms underlying the disorder or some relevant symptoms). The complexity of symptoms (positive, negative and cognitive) of schizophrenia makes it a very difficult task for a model to mimic all the main features of the disorder, but some rodent (mouse and rat) models have behavioural and even neurobiological phenotype characteristics resembling positive-like symptoms, cognitive symptoms and some neurochemical features of schizophrenia. As several recent works have already reviewed the main behavioural and developmental models, as well as the most used drug-induced, lesion-induced and genetic mouse models, the present review focuses on describing the most relevant genetically-based rat models of schizophrenia-relevant symptoms. Thus, we discuss several selective breeding programs leading to rat lines/strains which present impaired prepulse inhibition (PPI) of the acoustic startle response and (in some cases) latent inhibition deficits (both of which may be considered as endophenotypes of schizophrenia related with pre-attentive processes and attention, respectively), as well as other schizophrenia-relevant symptoms (e.g. learning deficits). Evidence is presented for the effects of genetic background on PPI (and other symptoms/phenotypes), as well as for environmental influences on genetic predisposition to enhanced apomorphine (mixed dopamine receptor agonist) effects. Some of the described rat models appear to present face validity and, to a certain extent, construct validity. While efforts should be made to evaluate the predictive validity of these genetic rat models, we propose that they have the advantage (over mouse knockouts, for example) of better representing "normal" genetic, neurobiological and phenotype variation, * Corresponding author.C. del Río et al. 262thus allowing the study of associations among them by means of genetic mapping or gene expression studies.

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Section: Selective Breeding Of Reduced Sensorimotor Gating: the Low-amentioning

confidence: 66%

Genetic Rat Models of Schizophrenia-Relevant Symptoms

Río¹,

Oliveras²,

Cañete³

et al. 2014

WJNS

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“…The neural basis of the startle reflex and the modulation of the reflex by prepulse stimuli have been extensively studied (33-37). Molecular factors underling the reflex and its alterations with specific diseases or treatments have also been reported (38, 39). Furthermore, prepulse inhibition of the startle reflex has been highlighted as one of the most reliable paradigms for evaluating sensorimotor gating (40).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Salicylate- and Quinine-Induced Tinnitus in Rats

Ralli¹,

Lobariñas²,

Fetoni³

et al. 2010

Otology &Amp; Neurotology

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Background-Salicylate and quinine have been shown to reliably induce short-term tinnitus when administered at high doses. The present study compared salicylate and quinine induced tinnitus in rats using the gap prepulse inhibition of acoustic startle (GPIAS).Methods-Twenty-four rats were divided into 2 groups; the first group (n=12) was injected with salicylate (300 mg/kg/d), the second (n=12) was treated with quinine orally at a dose of 200 mg/kg/ d. Animals were treated daily for 4 consecutive days. All rats were tested for tinnitus and hearing loss before and 2, 24, 48, 72, 96 hours after the first drug administration. Tinnitus was assessed using GPIAS; hearing function was measured with DPOAEs and ABR.Results-Salicylate treatment induced transient tinnitus with a pitch near 16 kHz starting 2 h posttreatment, persisting over the 4-day treatment period and disappearing 24 h later. Animals in the quinine group showed GPIAS changes at a higher pitch (20 kHz); however, changes were more variable among animals and the mean data were not statistically significant. Hearing function varied across treatments. In the salicylate group, high-level DPOAEs were slightly affected; most changes occurred 2 h post-treatment. Low-level DPOAEs were affected at all frequencies with a progressive dose-dependent effect. In the quinine group, only high-level DPOAEs were affected, mainly at 16 kHz.Conclusion-The present study highlights the similarities and differences in the frequency and the time course of tinnitus and hypoacusis induced by salicylate and quinine. Transient tinnitus was reliably induced pharmacologically with salicylate while hearing loss remained subclinical with only minor changes in DPOAEs.

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“…Prepulse inhibition is the phenomenon in which a preceding stimulus inhibits the reaction to a subsequent stronger startle stimulus. It is not necessarily related to social behavior, per se, but deficits in prepulse inhibition are observed in a variety of neuropsychiatric disorders of social dysfunction (Geyer et al, 1990; Perry et al, 2007), as well as in animal models of social dysfunction (Dieckmann et al, 2007; Koh et al, 2008). Prepulse inhibition may therefore be a reflection of not only attention and memory, but also social cognition, which may be partially regulated by AVP1A gene variants.…”

Section: Implications For Sex-specific Regulation Of Social Behavimentioning

confidence: 99%

Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior

Dumais

Veenema

2016

Frontiers in Neuroendocrinology

396

350

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The neuropeptides vasopressin (VP) and oxytocin (OT) and their receptors in the brain are involved in the regulation of various social behaviors and have emerged as drug targets for the treatment of social dysfunction in several sex-biased neuropsychiatric disorders. Sex differences in the VP and OT systems may therefore be implicated in sex-specific regulation of healthy as well as impaired social behaviors. We begin this review by highlighting the sex differences, or lack of sex differences, in VP and OT synthesis in the brain. We then discuss the evidence showing the presence or absence of sex differences in VP and OT receptors in rodents and humans, as well as showing new data of sexually dimorphic V1a receptor binding in the rat brain. Importantly, we find that there is lack of comprehensive analysis of sex differences in these systems in common laboratory species, and we find that, when sex differences are present, they are highly brain region- and species- specific. Interestingly, VP system parameters (VP and V1aR) are typically higher in males, while sex differences in the OT system are not always in the same direction, often showing higher OT expression in females, but higher OT receptor expression in males. Furthermore, VP and OT receptor systems show distinct and largely non-overlapping expression in the rodent brain, which may cause these receptors to have either complementary or opposing functional roles in the sex-specific regulation of social behavior. Though still in need of further research, we close by discussing how manipulations of the VP and OT systems have given important insights into the involvement of these neuropeptide systems in the sex-specific regulation of social behavior in rodents and humans.

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Disturbed social behavior and motivation in rats selectively bred for deficient sensorimotor gating

Cited by 28 publications

References 15 publications

Genetic Rat Models of Schizophrenia-Relevant Symptoms

Genetic Rat Models of Schizophrenia-Relevant Symptoms

Comparison of Salicylate- and Quinine-Induced Tinnitus in Rats

Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior

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