Karen E. Stevens

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A series of human and animal investigations has suggested that altered expression and function of the alpha7-nicotinic cholinergic receptor may be responsible for the auditory sensory gating deficit characterized in schizophrenia patients and their relatives as diminished suppression of an auditory-evoked response (P50) to repeated stimuli. This finding, in(More)
Activation of brain alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs) has broad therapeutic potential in CNS diseases related to cognitive dysfunction, including Alzheimer's disease and schizophrenia. In contrast to direct agonist activation, positive allosteric modulation of alpha7 nAChRs would deliver the clinically validated benefits of(More)
One function of the hippocampus is to ascertain the novelty of incoming sensations and encode significant new information into memory. The regulation of response to repeated stimuli may prevent overloading of this function by redundant sensory input. Recent pharmacological studies implicate the role of alpha-bungarotoxin-sensitive nicotinic cholinergic(More)
CONTEXT The alpha7 nicotinic acetylcholine receptor gene, CHRNA7, is associated with genetic transmission of schizophrenia and related cognitive and neurophysiological sensory gating deficits. Cognitive dysfunction is responsible for significant psychosocial disability in schizophrenia. Nicotine, a low-potency agonist at the alpha7 receptor, has some(More)
Rapid habituation of the evoked response to repeated auditory stimuli is a physiological manifestation of sensory gating mechanisms that are disturbed in human psychoses. Similar deficits are found in two animal models: fimbria-fornix lesioned Sprague-Dawley rats and DBA/2 mice, an inbred strain with decreased numbers of hippocampal alpha 7 nicotinic(More)
Patients with mental illness have a higher incidence of smoking than the general population and are the major consumers of tobacco products. This population includes subjects with schizophrenia, manic depression, depression, posttraumatic stress disorder (PTSD), attention-deficit disorder (ADD), and several other less common diseases. Smoking cessation(More)
Mice completely deficient for Dvl1, one of three mouse homologs of the Drosophila segment polarity gene Dishevelled, were created by gene targeting. Dvl1-deficient mice are viable, fertile, and structurally normal. Surprisingly, these mice exhibited reduced social interaction, including differences in whisker trimming, deficits in nest-building, less(More)
Dopaminergic and noradrenergic mediation of central sensory gating were assessed in Sprague-Dawley rats using a condition-test paradigm in which auditory evoked potentials were recorded. In this paradigm, unmedicated rats 'gate', i.e. suppress the response to the second of a pair of clicks delivered at a 0.5 s interval. Amphetamine-treated rats fail to(More)
OBJECTIVE Nicotinic acetylcholine receptors are possible therapeutic targets for schizophrenia, as shown by neurobiological and molecular evidence for deficiencies in expression of alpha(7)-nicotinic receptors. Patients' heavy smoking suggests attempted self-medication through this mechanism. The agent 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A) is a(More)
Sensory processing deficits are a hallmark of schizophrenia and can be demonstrated by recording auditory evoked potentials (AEPs) elicited in response to closely paired click stimuli. In nonschizophrenic humans, as well as in rats, the amplitude of the response to the second click is reduced (filtered) compared with the first. In contrast, schizophrenics,(More)