Some effects of Two Temporal Variables on Conditioned Suppression.
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Biomedical subjects
Publications and source records attributed to L Stein.
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Rats will self-administer dopamine D(1) and D(2) agonists, alone or in combination. Response rates and patterns for the D(1):D(2) combinations are nearly identical to those induced by cocaine. Here we examine whether rats prefer cocaine over D(1) or D(2) agonists presented alone or in D(1):D(2) combinations. During daily 3-h tests in a two-lever box, cocaine was available at either the right or left lever and the active side was alternated daily. After response rates had stabilized (+/-10% for 2 days), different groups were offered cocaine (800 microg/kg/injection) at one lever and either another dose (267, 1600, or 2400 microg/kg/injection) of cocaine or a dopamine agonist at the other lever. Animals consistently chose the higher of the presented cocaine doses over the low cocaine dose (267 microg). In choices between cocaine and dopamine agonists, the preferred cocaine dose (800 microg) was chosen over doses of the D(1) (SKF 82958) or D(2) ((+)-PHNO) agonist. However, no preference was shown between 800 microg cocaine and D(1):D(2) agonist mixtures, and the high-dose agonist mixture was preferred to the low cocaine dose. These results suggest that neither D(1) nor D(2) agonists alone fully duplicate the reinforcing actions of cocaine, but agonist combinations may approximate cocaine's reinforcement strength.
Using the hippocampal-slice preparation, we attempted to demonstrate operant conditioning of pyramidal cell activity using local micropressure applications of transmitters and drugs as reinforcement; the same injections administered independently of bursting provided a control for direct pharmacological stimulation or facilitation of firing. The results suggested that the spontaneous bursting of individual CA1 pyramidal neurons may be reinforced with activity-contingent injections of dopamine and cocaine, whereas, CA3-bursting responses may be reinforced with contingently-applied dynorphin A. We sought to confirm these indications of cellular reinforcement at the behavioral level in studies of hippocampal self-administration (despite the fact that the hippocampus has been ignored as a brain site for chemical self-administration experiments). The results suggested that dynorphin A is a powerful reinforcer of hippocampal self-administration behavior when injected in the CA3 field; experiments still in progress suggest that dopamine can reinforce self-administration behavior when injected in the CA1 field. Successful prediction of new behavioral data from operant-conditioning data at the cellular level helps to validate the cellular data by providing suggestive evidence of interrelationship between cellular and behavioral operant conditioning processes.
As a step towards comprehensive functional analysis of genomes, systematic gene knockout projects have been initiated in several organisms [1]. In metazoans like C. elegans, however, maternal contribution can mask the effects of gene knockouts on embryogenesis. RNA interference (RNAi) provides an alternative rapid approach to obtain loss-of-function information that can also reveal embryonic roles for the genes targeted [2,3]. We have used RNAi to analyze a random set of ovarian transcripts and have identified 81 genes with essential roles in embryogenesis. Surprisingly, none of them maps on the X chromosome. Of these 81 genes, 68 showed defects before the eight-cell stage and could be grouped into ten phenotypic classes. To archive and distribute these data we have developed a database system directly linked to the C. elegans database (Wormbase). We conclude that screening cDNA libraries by RNAi is an efficient way of obtaining in vivo function for a large group of genes. Furthermore, this approach is directly applicable to other organisms sensitive to RNAi and whose genomes have not yet been sequenced.
The 1982 Position Statement by the Joint Committee on Infant Hearing recommends that infants at risk for hearing impairment be screened by 3 mos of age and that the diagnostic process be completed an habilitation begun by 6 mos of age. How close to this ideal actual practice comes in an urban setting is the subject of this study, Data on 88 infants referred to a hospital-based parent-infant program were retrospectively examined to determine the occurrence of risk factors and at what ages: (1) hearing loss was first suspected, (2) hearing loss was diagnosed, and (3) habilitation was initiated. Results indicate that over one-quarter of all hearing-impaired infants will not manifest any of the risk factors proposed in the 1982 Position Statement and that regardless of whether the infant graduates from a neonatal intensive care unit or well-baby nursery, the median age for enrollment in a parent-infant program is a year or more later than the 1982 recommendation.
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OBJECTIVE: The purpose of this study was to determine whether the prevalence of current and past DSM-IV axis I psychiatric disorders is higher among persons with a history of exposure to organic solvents than among a demographically similar group of nonexposed control subjects. METHODS: Thirty-eight solvent-exposed subjects and 39 nonexposed healthy control subjects were evaluated for axis I disorder with the Structured Clinical Interview for DSM-IV. RESULTS: A significantly higher number of solvent-exposed subjects (71%) met criteria for current DSM-IV axis I disorder in comparison with control subjects (10%). The most prevalent diagnosis in exposed subjects was within the anxiety and mood clusters, with a high percentage (36%) of exposed subjects meeting criteria for a dual diagnosis of mood and anxiety disorder. There were no differences between the groups in past psychiatric disorders or current or past substance abuse or dependence. CONCLUSIONS: The rates of past psychiatric disorders among solvent-exposed subjects are similar to those among normal control subjects, but the prevalence of current DSM-IV axis I psychiatric disorders is significantly higher among exposed subjects than among control subjects.
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Twenty patients with failed back surgery syndrome were analyzed prospectively with MR imaging. In addition, 10 of these patients were analyzed with high-dose contrast-enhanced CT or gadopentetate dimeglumine-enhanced MR imaging. Imaging results were compared with surgical and pathologic findings in all cases. In the 10-patient subset, abnormal epidural soft-tissue specimens were also assessed with light and electron microscopy for vascular density, size of the extracellular space, and collagen orientation and thickness. The average vascular density of epidural fibrosis on light microscopy was found to be 1.19%; the average size of the extracellular space on electron microscopy was 4.29%. Scar 4 months of age or less had a larger extracellular space than did older scar; high- (grade 4 or 5) intensity scar had a larger extracellular space than did less intense scar on long TR/short TE images. Scar 1 year old or less enhanced more intensely on CT than did older scar. The MR signal intensity and CT enhancement characteristics of epidural scar were also found to differ according to epidural location. The percentage of scar that was hyperintense on long TR/TE images was as follows: anterior, 82%; lateral recess, 70%; lateral, 47%; and posterior, 20%. However, no relationship was found between the degree of CT enhancement of scar and vascular density. Gap junction status and extracellular space size, therefore, are more important than vascular density in predicting the degree of enhancement. The accuracy of contrast-enhanced CT and unenhanced MR in separating scar from herniated nucleus pulposus is 80%. This accuracy is related to the partial overlap in imaging characteristics of scar and recurrent herniated nucleus pulposus.