Animal Models of Obsessive-Compulsive Disorder: Strain Differences

Maio, Taimon P.; Filgueiras, Guilherme Bracarense; Cunha, Daniel C.; Estanislau, Célio

doi:10.4236/wjns.2014.43027

Cited by 4 publications

(6 citation statements)

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“…OCD exhibits a large behavioral repertoire with high rates of repetition and provides an ethological basis for studying compulsive-like behaviors in animal models of OCD [11]. Though inappropriate for investigating the entire OCD spectrum because obsessions cannot readily be assessed, animal models can provide deep insight into various forms of compulsivity [74]. …”

Section: Introductionmentioning

confidence: 99%

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Strain and sex based characterization of behavioral expressions in non-induced compulsive-like mice

Mitra

Bastos

Chesworth

et al. 2017

Physiology & Behavior

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There is currently a lack of understanding how genetic background and sex differences attribute to the heterogeneity of obsessive-compulsive disorder (OCD). An animal model of compulsive-like behaviors has been developed through bidirectional selection of house mice (Mus musculus) for high (big cotton nests; BIG mice) and low levels (small nests; SMALL mice) of nest-building behavior. The BIG male strains have predictive and face validity as a spontaneous animal model of OCD. Here, we evaluated compulsive-, anxiety-, cognitive-, and depression-like behaviors among male and proestrus female replicate strains each of BIG (BIG1, BIG2) and SMALL (SML1, SML2) nest-builders, and randomly-bred Controls (C1, C2). BIG1 and BIG2 males and females had higher nesting scores when compared to SMALL and Control strains. Male BIG1 and BIG2 strains showed more compulsive-like nesting than BIG1 and BIG2 proestrus females, which was not observed among the other strains. Nesting scores were also different between BIG replicate male strains. A similar pattern was observed in the compulsive-like marble burying behavior with BIG strains burying more marbles than SMALL and Control strains. Significant replicate and sex differences were also observed in marble burying among the BIG strains. The open field test revealed replicate effects while the BIG strains showed less anxiety-like behavior in the elevated plus maze test compared to the SMALL strains. For novel object recognition only the Control strains showed replicate and sex differences. In the depression-like forced swim test proestrus females demonstrated less depression-like behavior than males. BIG and SMALL nest-building strains had a higher corticosterone stress response than the Control strains. Together these results indicate a strong interplay of genetic background and sex in influencing expression of behaviors in our compulsive-like mouse model. These results are in congruence with the clinical heterogeneity of OCD.

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Section: Introductionmentioning

confidence: 99%

“…According to Maio et al [74], comparing our compulsive-like mouse strains is valuable for understanding the disorder. Compulsive-like behavior in our mice is defined as excessive and repetitive expression of otherwise normal behaviors, i.e., nest-building and marble burying.…”

Section: Introductionmentioning

confidence: 99%

Strain and sex based characterization of behavioral expressions in non-induced compulsive-like mice

Mitra

Bastos

Chesworth

et al. 2017

Physiology & Behavior

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“…The co morbid anxiety and cognitive functions associated with OCD during such a physiological state and the role of genetic background in influencing steroid actions demands investigation. According to Maio et al (2014), our mice developed through selective breeding for phenotypes of increased or decreased amounts of compulsive-like behavior can be a heuristic tool for studying OCD, especially the replicate BIG strains (BIG1 and BIG2). An unpublished study from our lab has shown that there is variation in compulsive-like and affective behaviors between the two replicate BIG strains that mimics heterogeneity as seen in subgroups of OCD patients.…”

Section: Introductionmentioning

confidence: 99%

Ovarian Sex Hormones Modulate Compulsive, Affective and Cognitive Functions in A Non-Induced Mouse Model of Obsessive-Compulsive Disorder

Mitra

Bastos

Bates

et al. 2016

Front. Behav. Neurosci.

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There is currently a lack of understanding of how surgical menopause can influence obsessions, compulsions and associated affective and cognitive functions in female obsessive-compulsive disorder (OCD) patients. Early menopause in women due to surgical removal of ovaries not only causes dramatic hormonal changes, but also may induce affective and cognitive disorders. Here, we tested if surgical removal of ovaries (ovariectomy, OVX), which mimics surgical menopause in humans, would result in exacerbation of compulsive, affective and cognitive behaviors in mice strains that exhibit a spontaneous compulsive-like phenotype. Female mice from compulsive-like BIG, non-compulsive SMALL and randomly-bred Control strains were subjected to OVX or sham-surgery. After 7 days animals were tested for nest building and marble burying to measure compulsive-like behavior. The elevated plus maze and open field tests measured anxiety-like behaviors, while memory was assessed by the novel object recognition. Acute OVX resulted in exacerbation of compulsive-like and anxiety-like behaviors in compulsive-like BIG mice. No significant effects of OVX were observed for the non-compulsive SMALL and Control strains. Object recognition memory was impaired in compulsive-like BIG female mice compared to the Control mice, without an effect of OVX on the BIG mice. We also tested whether 17 β-estradiol (E2) or progesterone (P4) could reverse the effects of OVX. E2, but not P4, attenuated the compulsive-like behaviors in compulsive-like BIG OVX female mice. The actions of the sex steroids on anxiety-like behaviors in OVX females were strain and behavioral test dependent. Altogether, our results indicate that already existing compulsions can be worsened during acute ovarian deprivation concomitant with exacerbation of affective behaviors and responses to hormonal intervention in OVX female mice can be influenced by genetic background.

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“…Obsessive Compulsive Disorder (OCD) is the most recognizable mental health condition that manifests such compulsions, which are also observed in cases of Tourette’s disorder, substance addiction, problematic internet usage, trichotillomania, pathological gambling, schizophrenia or eating disorders (DSM-5; American Psychiatric Association 2013 ; Fineberg et al 2018 ; Ioannidis et al 2016 ; Swets et al 2014 ). Compulsive behaviour can be shown in animal models of: (i) persistence to deal with adverse consequences; (ii) behavioural inflexibility; or, (iii) inability to stop behaviour (Maio et al 2014 ). Compulsive symptoms are commonly treated pharmacologically with selective serotonin reuptake inhibitors (SSRI) and antipsychotics (Fineberg et al 2010 ), and the fact that these drugs can reduce the compulsive behaviour mimicked by these models indicates predictive validity (Moreno and Flores 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Repeated Δ-9-Tetrahydrocannabinol administration dose dependently increases stablished schedule-induced drinking

Fuentes-Verdugo,

Pellón,

Miguéns

2024

Psychopharmacology

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Rationale Schedule-induced drinking (SID) reproduces an excessive and repetitive behavioural pattern that has led to propose this procedure as an animal model to study compulsive behaviours. Although it is known that cannabis can cause several adverse effects, in recent years there has been great interest in the medical application of cannabis derivatives for obsessive-compulsive related disorders. Objectives The present study investigated the effects of repeated THC administration on rates of previously acquired SID, as well as the possible alteration of its temporal distribution along inter-food intervals. Methods Male Wistar rats acquired SID under a 30 min fixed-time 30-sec food delivery schedule (from 30 to 43 sessions to reach a stable level). Thereafter, 5 or 10 mg/kg daily i.p. injections of THC or vehicle were repeatedly administered for 7 days to evaluate the effects on SID. Results Repeated THC administration at a dose of 5 mg/kg resulted in an increase on licking. Surprisingly, no effects on SID were observed with the 10 mg/kg dose. However, magazine entries were reduced with both THC doses. THC also modified the temporal distributions of licking and magazine entries during inter-food intervals. Conclusions The present results show that repeated THC administration may (i) increase induced licking at moderate doses, (ii) reduce magazine entries, and (iii) affect the temporal pattern of SID. These findings suggest that THC does not appear to be beneficial to reduce compulsive behaviour in this animal model, while another collateral effect of THC —such as a greater habitual-like behaviour— needs to be considered.

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Animal Models of Obsessive-Compulsive Disorder: Strain Differences

Cited by 4 publications

References 58 publications

Strain and sex based characterization of behavioral expressions in non-induced compulsive-like mice

Strain and sex based characterization of behavioral expressions in non-induced compulsive-like mice

Ovarian Sex Hormones Modulate Compulsive, Affective and Cognitive Functions in A Non-Induced Mouse Model of Obsessive-Compulsive Disorder

Repeated Δ-9-Tetrahydrocannabinol administration dose dependently increases stablished schedule-induced drinking

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