Background:Excessive checking is a common, debilitating symptom of obsessive–compulsive disorder. To further examine cognitive processes underpinning checking behaviour, and clarify how and why checking develops, we designed a novel operant paradigm for rats, the observing response task. The present study used the observing response task to investigate checking behaviour following excitotoxic lesions of the medial prefrontal cortex, nucleus accumbens core and dorsal striatum, brain regions considered to be of relevance to obsessive–compulsive disorder.Methods:In the observing response task, rats pressed an ‘observing’ lever for information (provided by light onset) about the location of an ‘active’ lever that provided food reinforcement. Following training, rats received excitotoxic lesions of the regions described above and performance was evaluated post-operatively before histological processing.Results:Medial prefrontal cortex lesions selectively increased functional checking with a less-prominent effect on non-functional checking and reduced discrimination accuracy during light information periods. Rats with nucleus accumbens core lesions made significantly more checking responses than sham-lesioned rats, including both functional and non-functional checking. Dorsal striatum lesions had no direct effect on checking per se, but reduced both active and inactive lever presses, and therefore changed the relative balance between checking responses and instrumental responses.Conclusions:These results suggest that the medial prefrontal cortex and nucleus accumbens core are important in the control of checking, perhaps via their role in processing uncertainty of reinforcement, and that dysfunction of these regions may therefore promote excessive checking behaviour, possibly relevant to obsessive-compulsive disorder.

Ancient legends described humans striving for self-improvement in areas such as immortality, excellence in sport or in rhetorical competitions (Gordijn, 2015). Today, self-enhancement can be observed in many domains: the use of cosmetics or cosmetic surgery to improve appearance, the use of interventions aiming at improving brain function and cognitive performance, also called neuroenhancement, and using doping for improving physical performance in athletics. This chapter aims at giving an overview of the recent history of neuroenhancement with a particular focus on ethical questions of neuroenhancement. Historically, tonics, herbs and other substances have in many cultures been used to improve general strength and endurance. Some examples are ma huang (Ephedra vulgaris) in China, Khat (Catha edulis) in Northern Africa, and coca (Erythroxylon coca) in South America (Angrist and Sudilovsky, 1978). Cocaine and amphetamine are modern cases of drugs initially enthusiastically acclaimed for enhancing cognition and mood. But in both cases, these initial Golden Periods were followed by a painful sobering, with the social and health-economic consequences still visible today. We want to portray these two, surprisingly parallel, stories shortly and then discuss the lessons learned (and further to be learned) from this from a regulatory and ethical perspective on the discussion on cognitive-(and mood-) enhancing drugs today. At least since the 6th century AD, coca leaves have been chewed in South America (Petersen and Stillman, 1977), initially for spiritual purposes and then as a resource to improve work performance in arduous circumstances (Petersen and Stillman, 1977). For various reasons (limited cocaine concentration in leaves, bitter taste), 'overindulgence', overdosing, or clear abuse and dependency in that population are rare (Carroll, 1977). In the mid-19th century (1870s and 1880s), researchers in North America and Europe isolated the main active ingredient, cocaine, and tested its effects in animals and humans, including in soldiers in Bavaria (Freud, 1885; Petersen and Stillman, 1977). In the influential essay 'On Coca', Sigmund Freud (1885: 298-304) praised cocaine as having a stimulating and enhancing effect, in part from his own experiences, and generally downplayed or even negated side effects, stating a desire to take higher and repeated doses. Freud recommended cocaine as a stimulant to enhance and maintain physical and mental performance. He also recommended it for various mental problems, including

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