Chronic lesions and ACTH: effects of thyroid hormones and electrical stimulation.
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Biomedical subjects
Publications and source records attributed to R Young.
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Psychoactive phenylisopropylamines can produce one or more of several different stimulus effects in animals. These effects are typified by the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), the central stimulant amphetamine, and by N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA), an agent whose actions are not yet well understood. The optical isomers of two phenylisopropylamines known to lack DOM and amphetamine-stimulus character, that is N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminobutane (MBDB) and 1-(3,4-dimethoxyphenyl)-2-aminopropane (3,4-DMA), were examined in rats trained to discriminate 1.25 mg/kg of PMMA from vehicle. The PMMA stimulus (ED(50)=0.4 mg/kg) generalized to all four agents: S(+)-MBDB (ED(50)=0.8 mg/kg), R(-)-MBDB (ED(50)=2.0 mg/kg), S(+)-3,4-DMA (ED(50)=2.6 mg/kg) and R(-)-3,4-DMA (ED(50)=3.9 mg/kg). The results show that these agents produce stimulus effects similar to those produced by PMMA. Both isomers of MBDB have been previously demonstrated to substitute for N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) in rats trained to discriminate MDMA from vehicle, but MBDB-trained animals failed to recognize DOM or amphetamine. Similar results were obtained with the 3,4-DMA optical isomers in the present investigation using rats trained to discriminate MDMA, DOM or (+)-amphetamine from vehicle; both isomers of 3,4-DMA substituted for an MDMA stimulus, but not for a DOM or amphetamine stimulus. Taken together, the evidence suggests that PMMA, S(+)-MBDB, R(-)-MBDB, S(+)-3,4-DMA, R(-)-3,4-DMA, and S(+)-MDMA can produce common stimulus effects in rats. The present findings also better define the PMMA stimulus and the structural requirements necessary to produce this type of stimulus effect.
alpha-Ethyltryptamine (alpha-ET) possesses central stimulant and hallucinogenic activity. Also, in tests of stimulus generalization using rats trained to discriminate the controlled substance analog (i.e., designer drug) N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) from vehicle, alpha-ET substituted for MDMA. These previous studies employed racemic alpha-ET. Because psychoactive phenylalkylamines with abuse potential can produce one or more of three distinct stimulus effects (i.e., amphetamine-, DOM- and/or PMMA-like effects) in animals trained to discriminate either the stimulant (+)amphetamine, the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), or N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA) from vehicle, and because these effects can be stereoselective, the individual optical isomers of alpha-ET were examined in groups of animals trained to discriminate (+)amphetamine, DOM, PMMA and MDMA from saline vehicle. (-)alpha-ET (ED(50)=7.8 mg/kg), but not (+)alpha-ET (maximum of 53% drug-appropriate responding), substituted for (+)amphetamine, whereas (+)alpha-ET (ED(50)=2.7 mg/kg), but not (-)alpha-ET (maximum of 33% drug-appropriate responding), substituted for DOM. Both optical isomers of alpha-ET substituted for PMMA and MDMA with ED(50) values of 1.6 and 1.4 mg/kg (PMMA-trained animals) and 1.3 and 2.0 mg/kg (MDMA-trained animals) for (-)alpha-ET and (+)alpha-ET, respectively. The results of this investigation suggest that both optical isomers of alpha-ET are capable of producing an MDMA/PMMA-like effect at nearly comparable doses, and that the stimulant or amphetamine-like nature of alpha-ET resides primarily with its (-)isomer whereas hallucinogenic or DOM-like character resides primarily with the (+)enantiomer.
The phenylisopropylamine PMMA or N-methyl-1-(4-methoxyphenyl)-2-aminopropane, a structural hybrid of paramethoxyamphetamine (PMA) and methamphetamine, has been previously shown to unexpectedly lack amphetamine-like or hallucinogen-like stimulus properties in animals. For example, in tests of stimulus generalization, neither a (+)amphetamine stimulus nor a DOM stimulus generalized to PMMA. It has also been shown, however, that stimulus generalization does occur in animals trained to discriminate the designer drug MDMA ("Ecstasy" or N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane) from vehicle. In order to further characterize this unique agent, we trained a group of six Sprague-Dawley rats to discriminate 1.25 mg/kg of PMMA (ED50 = 0.44 mg/kg) from saline vehicle. The PMMA stimulus failed to generalize to the phenylisopropylamine stimulant (+)amphetamine, or to the phenylisopropylamine hallucinogen DOM. Stimulus generalization occurred to (+/-)MDMA (ED50 = 1.32 mg/kg) and S(+)MDMA (ED50 = 0.48 mg/kg). Partial generalization occurred with R(+)MDMA, PMA, 3.4-DMA, and fenfluramine. The PMMA stimulus also generalized to the alpha-ethyl homolog of PMMA (EH/PMMA, ED50 = 1.29 mg/kg). Taken together, the results of these studies suggest that PMMA is an MDMA-like agent that lacks the amphetamine-like stimulant character of MDMA. These findings support our previous suggestion that PMMA be considered the structural parent of the MDMA-like family of designer drugs.
It has already been demonstrated that the psychoactive agent 1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDA) produces effects that are both hallucinogen-like and amphetamine or stimulant-like in animals. Hallucinogenic activity is associated primarily with the R(-)-isomer of MDA whereas stimulant activity is primarily associated with the S(+)-isomer. Because a previous report indicates that S(+)MDA fails to substitute for cocaine in rats trained to discriminate cocaine from vehicle, and because these findings are inconsistent with the purported stimulant nature of S(+)MDA, we reinvestigated the effect of both MDA isomers in rats. In this investigation, S(+)MDA doses of 1.25 and 1.5 mg/kg were found to produce > 80% cocaine-appropriate responding in rats trained to discriminate 8 mg/kg of cocaine from saline. However, consistent with a previous report, R(-)MDA resulted only in partial generalization. These new results support the hypothesis that the optical isomers of MDA produce distinguishable stimulus effects in rats and that S(+)MDA is the more stimulant isomer of MDA.
Research in the field of teenage drinking behavior has shown relationships between both social skills and drinking and alcohol expectancies and drinking. The present research investigated the comparative power of both of these sets of variables in predicting teenage drinking behavior, as well as looking at the contribution of more global cognitive structures. It was hypothesised that adolescents with high alcohol involvement would be discriminated from those with low involvement on the basis of social skills, cognitive structures, and alcohol expectancies. Seven hundred thirty-two adolescents participated in the study. Results indicated that adolescent alcohol involvement was associated with social skills deficits, positive alcohol expectancies, and negative cognitive structures concerning parents and teachers. The results revealed that, although the bulk of the variance in drinking behavior was explained by the independent effects of social skills and expectancies, the interaction of the two constructs explained an additional and significant proportion of the variance. Implications for preventive and treatment programs are discussed.
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Enteral feedings are often used to achieve adequate, cost-effective nutritional support. Placement of feeding tubes is accomplished by either a trained nurse or physician form a nutritional support team. A radiographic examination is required to confirm proper placement. These examinations are expensive and delay initiation of feeding while radiographs are taken and evaluated. A new enteral feeding tube (pH-FT) that incorporates a permanent pH-sensitive tip into a small-bore feeding tube has been developed. A detachable meter is used to monitor pH. This study was undertaken to determine if the pH-FT was reliable in determining placement as compared with radiograph interpretation. Twenty inpatients (14 males and six females) with diagnoses including major burn, trauma, and gastrointestinal disease were intubated with the use of pH-FT. Measurement of pH was taken at the time the radiographic examination was done. Reference pHs used include the following: stomach, 1.1 to 2.0; stomach in the presence of antacids/H2 blockers, 3.5 to 5.0; and the duodenal, 6.0 to 7.3. Of the 20 patients studied, there were four in whom the pH assessment indicated stomach placement with 100% radiograph confirmation. Sixteen patients had duodenal placement indicated by pH assessment, with radiograph confirmation in 88% (14) of the patients. Two patients had a pH indicating duodenal placement, and radiographic examination showed placement to the pH-FT in the stomach. Two benefits of the pH-FT would be decreased cost and earlier initiation of enteral feeding when the radiographic examination and interpretation are eliminated.
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