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Biomedical subjects

C F Shen

Publications and source records attributed to C F Shen.

5 recordsLinked to original sources

Robust and bootstrap testing procedures for bioequivalence.

A common problem encountered in bioequivalence studies is the presence of outliers. In this situation, the two one-sided t-tests proposed by Schuirmann fail to provide reasonable power for concluding bioequivalence. In contrast, our proposed 2 beta trimmed-t procedure has the following advantages: (1) it has higher efficiency for nonnormal symmetric distributions, (2) it is resistant to outliers, and (3) it is relatively easy to compute. Two bootstrap procedures introduced here provide further justification for the proposed trimmed t-test procedure. Results from Monte Carlo studies illustrate the power of the proposed procedures under various distributional assumptions for a 2 x 2 crossover trial.

Biological Availability

Centrally acting drugs act as conditioned stimuli in a conditioned suppression of drinking task.

An experiment was conducted to test whether centrally acting drugs could act as conditioned stimuli (CS) in a classical conditioning paradigm in which electric shock acted as the unconditioned stimulus (US) and suppression of drinking was used as an indicator of a conditioned response (CR). Thirsty rats were allowed to drink water during daily classical conditioning sessions which took place in their home cages. The CS was either a drug injected before the session or a "cocktail" of sensory stimuli (light + tone + vibration) turned on at the beginning of the session. Part way through some sessions the animals received electric foot shock as the US. Two different drugs and the sensory cocktail were used as CSs in a discriminated classical conditioning paradigm in which one drug or stimulus (the CS+) predicted the subsequent occurrence of shock, and the other two conditions acted as CS- stimuli and predicted absence of shock. After an average of 5.7 pairings of the CS+ with shock, conditioned suppression of drinking was observed; the CR occurred only during tests preceded by the CS+ drug or stimulus. At one time or another during the experiment, pentobarbital, phencyclidine, morphine, and pentylenetetrazol were employed as the CS+. Each acquired the ability to elicit a CR, although pentobarbital was noticeably less effective than the other three drugs. All conditioning trials took place in hanging metal cages, but the CR generalized into plastic cages with sawdust floors. Each rat received three successive phases of conditioning with a different CS+ condition employed in each phase; each phase of conditioning was followed by extinction of the CR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Discriminable effects of phencyclidine analogs evaluated by multiple drug (PCP versus OTHER) discrimination training.

This study tested structural analogs of phencyclidine (PCP) using drug discrimination procedures to determine which analogs produced discriminable effects similar to those of PCP. It also tested the utility of multiple-drug discrimination training (PCP versus other drugs or saline) as a method for increasing the specificity produced by training. All discrimination training took place in two-lever operant compartments using FR-10 reinforcement of presses on the correct lever. During training, rats were required to concurrently discriminate PCP from one or more other drug conditions. Rats in group 1 discriminated PCP (lever 1) versus saline (lever 2). Rats in group 2 discriminated PCP (lever 1) versus saline, fentanyl, phenobarbital, amphetamine, or mescaline (lever 2). In both groups 1 and 2, the required discriminations were rapidly learned. The percentage of PCP choices and the ED50 doses obtained during tests for generalization did not differ significantly in groups 1 and 2. Drugs to which responding on the PCP lever generalized included 1-[1-(2-thienyl)cyclohexyl]piperidine, N-ethyl-1-phenylcyclohexylamine, 1-phenylcyclohexylamine, ketamine, 1-(1-phenylcyclohexyl)morpholine, 1-[1-(2-thienyl)cyclohexyl]morpholine, N,N-diethyl-1-phenylcyclohexylamine, N-(iso-propyl)-1-phenylcyclohexylamine, N-methyl-1-phenylcyclohexylamine, N-(n-propyl)-1-phenylcyclohexylamine, Dextrorphan, (dl)-N-allyl-N-normetazocine, N-N-dimethyl-1-phenylcyclohexylamine, N-(n-butyl)-1-phenylcyclohexylamine, 1-[1-(2-thienyl)cyclohexyl]pyrrolidine, and N-(s-butyl)-1-phenylcyclohexylamine, in agreement with previous reports. Rats in group 3 discriminated PCP (lever 1) versus saline, cyclazocine, dextrorphan, phenobarbital, or mescaline (lever 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Comparison of four-drug discriminations in training compartments with four identical levers versus four different responses manipulanda.

Rats were trained to discriminate between four dissimilar drugs (phenobarbital, nicotine, fentanyl, and methylphenidate) in compartments which contained either four identical levers or four dissimilar response manipulanda. During successive training sessions, the drug condition was cycled through the four training conditions. The objective was to compare speed of acquisition and asymptotic accuracy of discriminative control in the following types of compartments: (1) Undecorated compartments with four identical levers; (2) Compartments with four dissimilar response manipulanda (lever, wheel, nosepoke, panel); (3) Four-lever compartments with a unique sensory environment surrounding each lever; (4) Compartments with four dissimilar manipulanda, each surrounded by a unique sensory environment. The required four-drug discrimination were learned in all training compartments. Independent variables that produced statistically significant effects on speed of acquisition and/or asymptotic accuracy included drug, dosage, use/nonuse of four dissimilar response manipulanda, and presence/absence of environmental decorations around each manipulandum. Although the use of four different response manipulanda and/or the use of distinctive decorations surrounding each of the four manipulanda did increase speed of acquisition, these manipulations also resulted in biases towards/against particular individual environments or manipulanda during the acquisition phase of the experiment. Such biases can complicate the interpretation of results of conventional drug discrimination studies, especially if they persist into the asymptotic accuracy phase, which was not observed in the present study.

Animals