Characterization of MK-801-induced behavior as a putative rat model of psychosis.
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The objective of this study was to characterize the behavior induced by the N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine maleate) in rats as a model of psychosis. The temporal profile, dose dependence, age, and sex differences of the behavior are described. A gas chromatographic method for the analysis of MK-801 in plasma and brain was developed. Female rats showed 4 to 10 times more MK-801-induced behavior and displayed around 25 times higher serum and brain concentrations of MK-801 than male rats. Twenty-one neuroactive compounds, including a number of excitatory amino acid-active substances, were tested for the effect on MK-801-induced behavior. Neuroleptics blocked MK-801-induced behavior in a dose-dependent manner that correlated to their antipsychotic potency in humans. Adenosine receptor agonists and an N-methyl-D-aspartate receptor-associated glycine site antagonist showed putative antipsychotic effects. In conclusion, MK-801-induced behavior represents a rat excitatory amino acid hypofunction model of psychosis that appears to be of clinical relevance and may be of value in the search for new antipsychotic agents. (+info)
Further analysis of problem behavior in response class hierarchies.
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A functional analysis identified the reinforcers for 3 participants' problem behavior, but only relatively mild problem behaviors (e.g., screaming, disruption) were observed when all topographies produced tested consequences. We then conducted an extinction analysis in which specific topographies produced a reinforcer while all other topographies were on extinction. The extinction analysis confirmed that the same reinforcer identified in the initial functional analysis maintained more severe topographies of problem behavior (e.g., aggression). In addition, results of the extinction analysis indicated that 2 of the participants displayed patterns of responding consistent with a response class hierarchy hypothesis, in which less severe problem behavior frequently occurred prior to more severe topographies. The 3rd participant displayed a response pattern indicative of differential reinforcement effects. (+info)
EphB2 guides axons at the midline and is necessary for normal vestibular function.
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Mice lacking the EphB2 receptor tyrosine kinase display a cell-autonomous, strain-specific circling behavior that is associated with vestibular phenotypes. In mutant embryos, the contralateral inner ear efferent growth cones exhibit inappropriate pathway selection at the midline, while in mutant adults, the endolymph-filled lumen of the semicircular canals is severely reduced. EphB2 is expressed in the endolymph-producing dark cells in the inner ear epithelium, and these cells show ultrastructural defects in the mutants. A molecular link to fluid regulation is provided by demonstrating that PDZ domain-containing proteins that bind the C termini of EphB2 and B-ephrins can also recognize the cytoplasmic tails of anion exchangers and aquaporins. This suggests EphB2 may regulate ionic homeostasis and endolymph fluid production through macromolecular associations with membrane channels that transport chloride, bicarbonate, and water. (+info)
Reinforcing variability in adolescents with autism.
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Five adolescents with autism, 5 adult control participants, and 4 child controls received rewards for varying their sequences of responses while playing a computer game. In preceding and following phases, rewards were provided at approximately the same rate but were independent of variability. The most important finding was that, when reinforced, variability increased significantly in all groups. Reinforced variability could provide the necessary behavioral substrate for individuals with autism to learn new responses. (+info)
Analyzing the multiple functions of stereotypical behavior for students with autism: implications for assessment and treatment.
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We studied behavioral functions associated with stereotypical responses for students with autism. In Study 1, analogue functional analyses (attention, demand, no-attention, and recreation conditions) were conducted for 5 students. Results suggested that stereotypy was multiply determined or occurred across all assessment conditions. For 2 students, stereotypy was associated with positive and negative reinforcement and the absence of environmental stimulation. For 2 other students, stereotypy occurred at high levels across all experimental conditions. For the 5th student, stereotypy was associated with negative reinforcement and the absence of environmental stimulation. In Study 2, the stereotypy of 1 student was further analyzed on a function-by-function basis. Within a concurrent-schedules procedure, alternative responses were taught to the student using functional communication training. The results of Study 2 showed that similar topographies of stereotypy, based on qualitatively different reinforcers, were reduced only when differential reinforcement contingencies for alternative forms of communication were implemented for specific response-reinforcer relations. Our results suggest that the causes of stereotypy for students with autism are complex and that the presumed association between response topography and behavioral function may be less important than previously realized. (+info)
Adrenergic hyperactivity and metanephrine excess in the nucleus accumbens after prefrontocortical dopamine depletion.
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Selective dopamine depletion within the medial prefrontal cortex in rats is known to enhance dopamine and norepinephrine levels in the nucleus accumbens and to induce characteristic behavioral disturbances. The present study was designed to determine levels of adrenaline, apart from dopamine and norepinephrine, and metabolites in the nucleus accumbens after prefrontocortical dopamine depletion. Prefrontocortical dopamine depletion was carried out by injecting 6-hydroxydopamine, and it was validated through: the emergence of behavioral disturbances such as amphetamine-induced stereotypies, spontaneous motor hyperactivity, and enhanced "anxiety-like" responses and through postmortem quantification of catecholamine levels by using high-performance liquid chromatography. The findings indicated that lesioned rats exhibited more oral stereotypies after amphetamine, were hyperlocomotive, and showed more pronounced anxiety-like behaviors than controls. Following prefrontocortical dopamine depletion, postmortem concentrations of dopamine and norepinephrine, along with the metabolites 3,4-dihydroxyphenylacetic acid and vanillylmandelic acid, were reliably enhanced in the nucleus accumbens as expected, and dopamine turnover was decreased. Furthermore the nucleus accumbens contained higher levels of adrenaline and its transmethylated metabolite metanephrine. To sum up, prefrontocortical dopamine depletion induces motor and emotional disturbances in rats and alters the neurochemical profile of the nucleus accumbens, not only inducing dopaminergic and noradrenergic hyperactivity but also leading to adrenaline and metanephrine excess. (+info)
Further evaluation of the role of protective equipment in the functional analysis of self-injurious behavior.
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Using a procedure similar to the one described by Le and Smith (in press), we evaluated the effects of protective equipment during a functional analysis for 2 individuals who engaged in severe self-injurious behavior (SIB). Results of our analyses revealed that the use of protective equipment during functional analyses of SIB suppressed levels of responding such that a behavioral function could not be identified. (+info)
Conditions of application of repeated transcranial magnetic stimulation to rats may mask the effects of the treatment.
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Rats of sham repeated transcranial magnetic stimulation (rTMS) group, kept in noisy room and transiently immobilized (5 min) for 12 consecutive days, showed similar inhibition of body weight gain, increase in exploratory locomotor activity, and elevation of motor response to apomorphine as rats undergoing magnetic stimulation of the brain, and had only slightly lower response in apomorphine stereotypy. Some of the responses ascribed to antidepressant action of rTMS in animal experiment may be due to environmental conditions, and not alternating magnetic field passing the brain. (+info)