Negative valence system as a relevant domain in compulsivity: review in a preclinical model of compulsivity

Abstract

Compulsive behavior is observed in different neuropsychiatric disorders such as Obsessive-Compulsive Disorder (OCD), anxiety, phobia, schizophrenia and addiction. Compulsivity has been proposed as a transdiagnostic symptom, where the Research Domain Criteria (RDoC) strategy could help to understand its neuropsychological basis for a better understanding, and development of therapeutic and preventive strategies. However, research on compulsivity has been focused on the cognitive control domain, and the contribution of an altered negative valence system has been less considered. In this review, we collate the main findings in an animal model of compulsivity, the high drinker (HD) rats selected by Schedule-Induced Polydipsia (SIP) regarding these two research domains. This preclinical model of compulsivity has shown a phenotype characterized by a lack of behavioral inhibition, impulsive decision-making and cognitive inflexibility. Moreover, the results in compulsive HD rats, suggests that there is also a relevant alteration in the emotional dimension, linked to the negative valence system domain, as for example by: the increased perseverative responses in a withdrawal condition, associated with the behavioral construct of frustrative non-reward; and an inhibition or extinction deficit in memory retrieval associated with an alteration in the behavioral response to sustained threat. However, the precise nature of the link between these shared altered domains, cognitive control and negative valence system, remains unknown. These results point towards relevant behavioral aspects of the compulsive phenotype that should be taken into account when studying the vulnerability to compulsivity that could help in the development of a better transdiagnostic assessment, preventive and therapeutic strategies.

Mapping the neuroanatomical abnormalities in a phenotype of male compulsive rats

“…Please, note that the effect showed on SIP between HD and LD groups might not be due to a difference in motivation or reward processing, as both groups did not show differences in magazine entries. Therefore, these differences are associated to the performance of excessive and persistent drinking behavior, measured by water consumed and licking behavior on SIP (For a review see [ 60 , 73 , 74 ].

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Behavioral domains in compulsive rats: implications for understanding compulsive spectrum disorders

“…Second, the correlation analysis performed shows a potential relationship between the behavioral domains assessed. However, further studies might analyze the microstructural differences in some types of behaviors, disentangling whether the differences between groups depend on how LD and HD learn to seek or to avoid negative contingencies, highlighting the relationship between cognitive control and negative valence system domains on the development of compulsive behaviors (Moreno-Montoya et al, 2022 ). Indeed, increasing the sample size would also help to improve the assessment and use of an integrative statistical approach across all tasks.…”

“…There is a growing interest in the RDoC initiative, highlighting the importance of identifying the behavioral and cognitive domains related to compulsive behavior. However, this characterization has been mainly based on cognitive domains, excluding other important information related to emotional processing, which could lead to a better characterization of possible endophenotypes (Moreno-Montoya et al, 2022 ).…”

“…In this sense, drinking behavior on SIP is (1) excessive, because the amount of water ingested reaches in some cases one-half of their body weight in water (Falk, 1966 ); (2) persistent across the session and despite negative consequences such as when water is substituted by quinine (Fouyssac et al, 2021 ); and (3) maladaptive behavioral habit, as it is not a result of physiological needs (Falk, 1961 , 1966 , 1971 ). Thus, SIP preclinical model allows us to identify a compulsive vulnerable population to study behavioral (Moreno-Montoya et al, 2022 ) and neurochemical alterations (Martín-González et al, 2022a ) to extend our knowledge of common compulsive spectrum disorders due to their transdiagnostic profile as, for example, in addiction, schizophrenia, or OCD (Moreno and Flores, 2012 ; Belin-Rauscent et al, 2016 ; Navarro et al, 2017 ).…”

Phenomenological Considerations of the World of the Obsessive Patient

“…In the DSM-5, OCD is recognized within the specific diagnostic category of obsessive-compulsive and related disorders; this deviates from its previous classification within anxiety disorders [ 9 ], reflecting scientific advances [ 10 , 11 , 12 , 13 , 14 ]. However, OCD remains a disorder with paradoxical psychological and behavioral symptoms [ 15 , 16 ] (i.e., ‘certain thoughts can lead to catastrophic events’, ‘thinking of doing something is equivalent to doing it’, and ‘not preventing something is equivalent to causing it’).…”