Development and temporal organization of compulsive checking induced by repeated injections of the dopamine agonist quinpirole in an animal model of obsessive-compulsive disorder

Dvorkin, Anna; Perreault, Melissa L.; Szechtman, Henry

doi:10.1016/j.bbr.2006.01.024

Cited by 29 publications

(97 citation statements)

References 27 publications

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“…This is consistent with previous research, which has established that repeated exposure to quinpirole produces a characteristic response pattern in rats that includes an initial suppression of locomotor activity, followed by a gradual increase in activity over several days (Foley, Fudge, Kavaliers, & Ossenkopp 2006). This is known as behavioral sensitization, wherein the behavioral response to a given dose of quinpirole tends to increase across repeated exposure to the drug (Dvorkin, Perreault, & Szechtman, 2006). When rates of lever pressing were pooled across sessions and the baseline and operant phases were compared, the drug-treated animals displayed fewer presses per day during the operant phase (M ¼ 260.24, SD ¼ 80.12) than during the baseline phase (M ¼ 397.73, SD ¼ 42.26), as a result of the initial suppression of locomotor activity that occurs when drug-naive animals are first exposed to quinpirole, paired-samples t test, t(11) ¼ 5.62, p < .001.…”

Section: Resultssupporting

confidence: 92%

Contrafreeloading in Rats Is Adaptive and Flexible: Support for an Animal Model of Compulsive Checking

Frederick

Cocuzzo

2017

Evol Psychol

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Contrafreeloading involves working unnecessarily to obtain a reward that is otherwise freely available. It has been observed in numerous species and can be adaptive when it provides an organism with updated information about available resources. Humans frequently update their knowledge of the environment through checking behaviors. Compulsive checking occurs when such actions are performed with excessive frequency. In a putative animal model of compulsive checking, rats treated chronically with the dopamine agonist quinpirole display exaggerated contrafreeloading for water. Although this effect has been attributed to behavioral rigidity, some evidence suggests the behavior remains somewhat flexible and may be adaptive under certain conditions. We assessed the ability of quinpirole-treated rats with contrafreeloading experience to adapt to changing contingencies by requiring them to alternate between response levers. Rats treated with quinpirole or saline were first trained to obtain water by pressing either of two levers. Next, free water was made available for 8 days, and contrafreeloading was measured. Rates of contrafreeloading were significantly higher in the drug-treated rats than in controls. On the following 5 days, each reward caused the associated lever to become inactive until a reward was earned from the alternate lever. Quinpirole-treated rats learned this new response requirement more quickly than controls. Thus, exaggerated checking behavior induced by chronic quinpirole treatment can be advantageous when environmental contingencies change. These results provide support for this animal model of compulsive checking and hint at the presence of a specialized neural checking module involving the dopamine system.

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Section: Resultssupporting

confidence: 92%

Contrafreeloading in Rats Is Adaptive and Flexible: Support for an Animal Model of Compulsive Checking

Frederick

Cocuzzo

2017

Evol Psychol

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“…EthoVision 3.1 software was used to extract the time series of the x, y coordinates of the rat from digitized video recordings (Dvorkin et al 2006). Digitized tracking data were preprocessed to remove noise (by applying appropriate filters to smooth the x, y coordinates) (Hen et al 2004), and the obtained coordinates were divided into episodes of forward locomotion (called progression) and episodes of small movements or immobility (called lingering), as described previously (Drai et al 2000;Drai and Golani 2001;Golani et al 1993).…”

Section: Discussionmentioning

confidence: 99%

“…These doses of mCPP were chosen because they produce compulsive-like behavior in a rat model (Kontis et al 2008). (−)-Quinpirole hydrochloride was administered at a dose of 0.125 mg/kg (rather than 0.5 mg/kg; Dvorkin et al 2006;Szechtman et al 1998) to minimize the possibility that a full dose of quinpirole produces a ceiling effect on compulsive checking that would mask a potential exacerbation with mCPP cotreatment. All drugs were dissolved in 0.9 % physiological saline and administered at a volume of 1 ml/kg through a subcutaneous injection under the nape of the neck.…”

Section: Drugsmentioning

confidence: 99%

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Effects of the serotonergic agonist mCPP on male rats in the quinpirole sensitization model of obsessive–compulsive disorder (OCD)

et al. 2013

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“…Temporal data potentially provide information about a satiety state because within a motivational framework the existence of excessively long inter-bout intervals points to the operation of a second process; for instance, the short intra-eating intervals within a meal appear controlled by a process such as hunger while the long inter-meal intervals are said to reflect the operation of a satiety mechanism (Tolkamp et al, 1998;Tolkamp and Kyriazakis, 1999;Yeates et al, 2001). Interestingly, we reported recently that in an animal model of OCD, there exists a paucity of long intervals between bouts of checking behavior, consistent with a diminished sense of satiety (Dvorkin et al, 2006). A similar examination of the temporal dynamics of rituals shown by OCD patients seems warranted.…”

Section: An Approach To Identifying the Dysfunctional Component Or Comentioning

confidence: 95%

Obsessive-compulsive disorder as a disturbance of security motivation: Constraints on comorbidity

Szechtman

Woody

2006

neurotox res

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Patients with OCD often meet criteria for additional psychiatric disorders, with the incidence of comorbidity being as high as 75% in some studies. Here we examine the theoretical plausibility that in OCD much of the domain of co-morbid presentations encompasses related perturbations of the security motivation system. According to a recent proposal, the security motivation system represents a biologically primitive special motivation that is activated by potential (as opposed to imminent) danger to self or intimate others and engages a set of specialized species-typical behaviors (such as checking and washing) to handle potential danger. Because the task of security motivation is open ended, in the sense that no consummatory stimuli can exist in the real world to indicate the absence of potential danger, the shutdown of security motivation is produced by a self-generated feeling of knowing, a satiety signal termed yedasentience. In this schema, OCD results from a failure to generate or respond to the yedasentience signal: without this negative feedback the patient persists abnormally long in a strong motivational state having to do with primal, basic threats to existence, a condition that leads to prolonged engagement in security-related behaviors, such as the checking and washing, characteristic of OCD compulsions and obsessions. Considering the proposed neuronatomy of security motivation system and OCD, we discuss the likelihood that the phenomenon of "spread of allied reflexes" can produce other security-related psychiatric conditions, as well as the possibility that disturbances along different pathways of the security motivation system can lead to apparently different disorders.

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Development and temporal organization of compulsive checking induced by repeated injections of the dopamine agonist quinpirole in an animal model of obsessive-compulsive disorder

Cited by 29 publications

References 27 publications

Contrafreeloading in Rats Is Adaptive and Flexible: Support for an Animal Model of Compulsive Checking

Contrafreeloading in Rats Is Adaptive and Flexible: Support for an Animal Model of Compulsive Checking

Effects of the serotonergic agonist mCPP on male rats in the quinpirole sensitization model of obsessive–compulsive disorder (OCD)

Obsessive-compulsive disorder as a disturbance of security motivation: Constraints on comorbidity

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