Strain differences in ‘compulsive’ lever-pressing

Brimberg, Lior; Flaisher-Grinberg, Shlomit; Schilman, Eduardo A.; Joel, Daphna

doi:10.1016/j.bbr.2007.01.014

Cited by 19 publications

(12 citation statements)

References 31 publications

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“…For instance, the Flinders Sensitive rats line has been used as a model for depression (Overstreet, 1986) and the Alcohol Preferring P rats have been used as a model for alcoholism (Penn et al, 1978). Lewis rats have been used to study the biological mechanisms underlying obsessive compulsive disorder (Brimberg et al, 2007) and Fischer 344 and Lewis rats have been used to study susceptibility to psychoactive drugs and to stress (Suzuki et al, 1988; Cohen et al, 2006). Strain differences have been suggested as a method to define predictive responses to current medications (Porsolt et al, 1978; Gould et al, 2007) and to select appropriate animals for behavioral models of specific disorders and as background for the development of animal with targeted mutations (Crawley, 1999; Gould et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Strain-specific battery of tests for domains of mania: effects of valproate, lithium and imipramine

Flaisher-Grinberg

Einat

2010

Front. Psychiatry

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The lack of efficient animal models for bipolar disorder (BPD), especially for the manic pole, is a major factor hindering the research of its pathophysiology and the development of improved drug treatments. The present study was designed to identify an appropriate mouse strain for modeling some behavioral domains of mania and to evaluate the effects of drugs using this strain. The study compared the behavior of four strains: Black Swiss, C57Bl/6, CBA/J and A/J mice in a battery of tests that included spontaneous activity; sweet solution preference; light/dark box; resident-intruder; forced-swim and amphetamine-induced hyperactivity. Based on the ‘manic-like’ behavior demonstrated by the Black Swiss strain, the study evaluated the effects of the mood stabilizers valproate and lithium and of the antidepressant imipramine in the same tests using this strain. Results indicated that lithium and valproate attenuate the ‘manic-like’ behavior of Black Swiss mice whereas imipramine had no effects. These findings suggest that Black Swiss mice might be a good choice for modeling several domains of mania and distinguishing the effects of drugs on these specific domains. However, the relevance of the behavioral phenotype of Black Swiss mice to the biology of BPD is unknown at this time and future studies will investigate molecular differences between Black Swiss mice and other strains and asess the interaction between strain and mood stabilizing treatment.

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Section: Discussionmentioning

confidence: 99%

Strain-specific battery of tests for domains of mania: effects of valproate, lithium and imipramine

Flaisher-Grinberg

Einat

2010

Front. Psychiatry

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“…Haloperidol (VetMarket) and paroxetine (Unipharm, Ramat-Gan, Israel) were prepared as previously described (Brimberg et al, 2007;Joel and Doljansky, 2003), and injected i.p. 60 and 30 min, respectively, before behavioral assessment.…”

Section: Drugsmentioning

confidence: 99%

Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders

Brimberg

Benhar

Mascaro-Blanco

et al. 2012

Neuropsychopharmacol

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178

198

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Group A streptococcal (GAS) infections and autoimmunity are associated with the onset of a spectrum of neuropsychiatric disorders in children, with the prototypical disorder being Sydenham chorea (SC). Our aim was to develop an animal model that resembled the behavioral, pharmacological, and immunological abnormalities of SC and other streptococcal-related neuropsychiatric disorders. Male Lewis rats exposed to GAS antigen exhibited motor symptoms (impaired food manipulation and beam walking) and compulsive behavior (increased induced-grooming). These symptoms were alleviated by the D2 blocker haloperidol and the selective serotonin reuptake inhibitor paroxetine, respectively, drugs that are used to treat motor symptoms and compulsions in streptococcal-related neuropsychiatric disorders. Streptococcal exposure resulted in antibody deposition in the striatum, thalamus, and frontal cortex, and concomitant alterations in dopamine and glutamate levels in cortex and basal ganglia, consistent with the known pathophysiology of SC and related neuropsychiatric disorders. Autoantibodies (IgG) of GAS rats reacted with tubulin and caused elevated calcium/calmodulindependent protein kinase II signaling in SK-N-SH neuronal cells, as previously found with sera from SC and related neuropsychiatric disorders. Our new animal model translates directly to human disease and led us to discover autoantibodies targeted against dopamine D1 and D2 receptors in the rat model as well as in SC and other streptococcal-related neuropsychiatric disorders.

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“…In the Test, paroxetine dose-dependently decreased the number of ELP-C ( Figure 1A; ANOVA yielded a significant main effect of Dose, F ( Mean and standard error of the number of extra lever presses that (A) were followed by magazine entry (extra lever presses in completed trials; ELP-C) and (B) were not followed by magazine entry (extra lever presses in uncompleted trials; ELP-U) of rats treated with vehicle or 1, 5 or 10 mg/kg of paroxetine on the test day of the PTSA procedure. Re-printed with permission from 52 .…”

Section: Representative Resultsmentioning

confidence: 99%

Signal Attenuation as a Rat Model of Obsessive Compulsive Disorder

Goltseker

Yankelevitch-Yahav

Albelda

et al. 2015

JoVE

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In the signal attenuation rat model of obsessive-compulsive disorder (OCD), lever-pressing for food is followed by the presentation of a compound stimulus which serves as a feedback cue. This feedback is later attenuated by repeated presentations of the stimulus without food (without the rat emitting the lever-press response). In the next stage, lever-pressing is assessed under extinction conditions (i.e., no food is delivered). At this stage rats display two types of lever-presses, those that are followed by an attempt to collect a reward, and those that are not. The latter are the measure of compulsive-like behavior in the model. A control procedure in which rats do not experience the attenuation of the feedback cue serves to distinguish between the effects of signal attenuation and of extinction. The signal attenuation model is a highly validated model of OCD and differentiates between compulsive-like behaviors and behaviors that are repetitive but not compulsive. In addition the measures collected during the procedure eliminate alternative explanations for differences between the groups being tested, and are quantitative, unbiased and unaffected by inter-experimenter variability. The major disadvantages of this model are the costly equipment, the fact that it requires some technical know-how and the fact that it is time-consuming compared to other models of OCD (11 days). The model may be used for detecting the anti-or pro-compulsive effects of pharmacological and non-pharmacological manipulations and for studying the neural substrate of compulsive behavior.

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Strain differences in ‘compulsive’ lever-pressing

Cited by 19 publications

References 31 publications

Strain-specific battery of tests for domains of mania: effects of valproate, lithium and imipramine

Strain-specific battery of tests for domains of mania: effects of valproate, lithium and imipramine

Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders

Signal Attenuation as a Rat Model of Obsessive Compulsive Disorder

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