Rats treated chronically with the dopamine agonist quinpirole (0.5 mg/kg, twice weekly X 10) met 5 criteria for performance of compulsive checking. Specifically, in a large open-field with single small objects in 4 of 25 locales, quinpirole rats revisited two places/objects excessively often and rapidly, compared with other locations in the environment or saline controls. They performed a ritual-like set of behavioral acts at these two places/objects and stopped in relatively few locales before returning to the preferred places/objects. Finally, they shifted their behavior to a new location when the object was moved there. Clomipramine (10 mg/kg, daily) postponed but did not prevent the development of the quinpirole effect. Quinpiroleinduced compulsive checking may be an exaggeration of normal checking of home site in rats.Results suggest an animal model of obsessive-compulsive disorder and a role for dopamine in this disorder.

The authors hypothesize that the symptoms of obsessive-compulsive disorder (OCD), despite their apparent nonrationality, have what might be termed an epistemic origin-that is, they stem from an inability to generate the normal "feeling of knowing" that would otherwise signal task completion and terminate the expression of a security motivational system. The authors compare their satiety-signal construct, which they term yedasentience, to various other senses of the feeling of knowing and indicate why OCD-like symptoms would stem from the abnormal absence of such a terminator emotion. In addition, they advance a tentative neuropsychological model to explain its underpinnings. The proposed model integrates many previous disparate observations and concepts about OCD and embeds it within the broader understanding of normal motivation.

The objective of this review is to identify a target or biomarker of altered neurochemical sensitivity that is common to the many animal models of human psychoses associated with street drugs, brain injury, steroid use, birth injury, and gene alterations. Psychosis in humans can be caused by amphetamine, phencyclidine, steroids, ethanol, and brain lesions such as hippocampal, cortical, and entorhinal lesions. Strikingly, all of these drugs and lesions in rats lead to dopamine supersensitivity and increase the high-affinity states of dopamine D2 receptors, or D2High, by 200-400% in striata. Similar supersensitivity and D2High elevations occur in rats born by Caesarian section and in rats treated with corticosterone or antipsychotics such as reserpine, risperidone, haloperidol, olanzapine, quetiapine, and clozapine, with the latter two inducing elevated D2High states less than that caused by haloperidol or olanzapine. Mice born with gene knockouts of some possible schizophrenia susceptibility genes are dopamine supersensitive, and their striata reveal markedly elevated D2High states; suchgenes include dopamine-beta-hydroxylase, dopamine D4 receptors, G protein receptor kinase 6, tyrosine hydroxylase, catechol-O-methyltransferase, the trace amine-1 receptor, regulator of G protein signaling RGS9, and the RIIbeta form of cAMP-dependent protein kinase (PKA). Striata from mice that are not dopamine supersensitive did not reveal elevated D2High states; these include mice with knockouts of adenosine A2A receptors, glycogen synthase kinase GSK3beta, metabotropic glutamate receptor 5, dopamine D1 or D3 receptors, histamine H1, H2, or H3 receptors, and rats treated with ketanserin or aD1 antagonist. The evidence suggests that there are multiple pathways that convergetoelevate the D2High state in brain regions and that this elevation may elicit psychosis. This proposition is supported by the dopamine supersensitivity that is a common feature of schizophrenia and that also occurs in many types of genetically altered, drug-altered, and lesion-altered animals. Dopamine supersensitivity, in turn, correlates with D2High states. The finding that all antipsychotics, traditional and recent ones, act on D2High dopamine receptors further supports the proposition.

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An auditory hallucination shares with imaginal hearing the property of being self-generated and with real hearing the experience of the stimulus being an external one. To investigate where in the brain an auditory event is ''tagged'' as originating from the external world, we used positron emission tomography to identify neural sites activated by both real hearing and hallucinations but not by imaginal hearing. Regional cerebral blood f low was measured during hearing, imagining, and hallucinating in eight healthy, highly hypnotizable male subjects prescreened for their ability to hallucinate under hypnosis (hallucinators). Control subjects were six highly hypnotizable male volunteers who lacked the ability to hallucinate under hypnosis (nonhallucinators). A region in the right anterior cingulate (Brodmann area 32) was activated in the group of hallucinators when they heard an auditory stimulus and when they hallucinated hearing it but not when they merely imagined hearing it. The same experimental conditions did not yield this activation in the group of nonhallucinators. Inappropriate activation of the right anterior cingulate may lead self-generated thoughts to be experienced as external, producing spontaneous auditory hallucinations.

Even with the enhanced emotional salience of facial stimuli, adults with autism showed lower activity in the fusiform cortex and differed from the comparison subjects in activation of other brain regions. The authors suggested that the recognition of emotion by adults with autism is achieved through recruitment of brain regions concerned with allocation of attention, sensory gating, the referencing of perceptual knowledge, and categorization.

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