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Biomedical subjects

M G Paule

Publications and source records attributed to M G Paule.

97 records · Page 6Linked to original sources
PubMedDate not supplied

Symposium overview: the use of delayed matching-to-sample procedures in studies of short-term memory in animals and humans.

Behavioral paradigms applicable for use in both human and nonhuman subjects for investigating aspects of working/short-term memory are presented with a view towards exploring their strengths, weaknesses, and utility in a variety of experimental situations. Such procedures can be useful in teasing out specific aspects of mnemonic processes including discrimination, encoding, and retention. Delayed matching-to-position, delayed matching-to-sample (DMTS), and titrating matching-to-sample procedures are highlighted. Additionally, the application of DMTS tasks in preclinical and clinical settings is presented: drug effects on memory processes can be explored preclinically in animal models; normative data have been developed in human populations where they have been used in adults to explore the relationships between mnemonic processes and specific clinical entities such as Parkinsonism, senile dementia of the Alzheimer's type, schizophrenia, and depression. Studies in children indicate that encoding and retention processes improve rapidly in the early years, plateauing prior to puberty. Noninvasive imaging techniques such as positron emission tomography (PET) indicate that activity in specific brain areas is associated with DMTS task performance and may serve to confirm roles for such structures in mnemonic processes.

Animals↗
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Operant test battery performance in children: correlation with IQ.

The relationship between intelligence and money-(nickel-)reinforced operant behaviors were compared in 115 six year old children. The Operant Test Battery (OTB) consists of tasks thought to engender responses dependent upon specific brain functions that include motivation, color and position discrimination, learning, short-term memory, and time estimation. OTB endpoints were compared with Full Scale, Verbal and Performance IQ scores. Highly significant correlations were noted between several OTB measures (e.g., color and position discrimination accuracy) and IQ scores, but not in others (e.g., motivation task response rate). The results demonstrate the relevance of these measures as metrics of important brain functions. Additionally, since laboratory animals can readily perform these same tasks, these kinds of behaviors in laboratory animals should be useful in studying the effects of neuroactive/neurotoxic compounds on aspects of cognitive function in animals and in predicting adverse effects of such agents on related brain functions in humans.

Brain↗
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The use of timing behaviors in animals and humans to detect drug and/or toxicant effects.

Behavioral paradigms applicable for use in both human and nonhuman subjects for investigating aspects of timing behavior are presented with a view towards exploring their strengths, weaknesses, and utility in a variety of experimental situations. Tri-peak, peak interval, differential reinforcement of low rate responding, and temporal response differentiation procedures are highlighted. In addition, the application of timing tasks in preclinical and clinical settings is discussed: pharmacological manipulations are providing information on the neurotransmitters involved and species differences; normative data for children are being developed; and noninvasive imaging procedures are being employed in adult human subjects to explore the involvement of specific brain areas.

Animals↗
PubMedDate not supplied

Adaptation of a primate operant test battery to the rat: effects of chlorpromazine.

The National Center for Toxicological Research (NCTR) Operant Test Battery (OTB) has been used extensively in rhesus monkeys to characterize the effects of drugs and toxicants on the performance of tasks designed to model several cognitive functions. Recently, the majority of the OTB tasks have been adapted for use in rats. The current study is the first to examine the effects of a prototypic pharmacological agent previously assessed in monkeys on rat OTB performance. The effects of the dopamine antagonist chlorpromazine (0.56-5.6 mg/kg, i.p.) were assessed in rats performing tasks designed to model auditory-visual-position discrimination, learning, time estimation, and appetitive motivation. All four tasks were equally sensitive to the behavioral effects of chlorpromazine. This pattern of sensitivity was very similar to that obtained when chlorpromazine was tested in monkeys performing the OTB. These data thus suggest that operant tasks designed to model cognitive functions in monkeys can also be used in rats, and that the effects of chlorpromazine on the performance of these tasks may be predictive of results obtained with monkeys. Further characterization of the rat OTB using prototypic pharmacological agents will further determine the extent to which drug effects on rat OTB performance can be generalized to primates.

Animals↗
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Effects of trimethyltin on incremental repeated acquisition (learning) in the rat.

The effects of the neurotoxicant, trimethyltin (TMT), on the acquisition of serial position response chains (learning) in adult rats were examined. Animals performing incremental repeated acquisition tasks for food were injected once with either 7.5 or 8.7 mg/kg TMT, IP. TMT decreased efficiencies (correct/total responses) in all 5 subjects; maximal decrements occurred 1-3 weeks post-treatment. Efficiency in 3 rats returned to pre-TMT levels within 5 weeks; values for the other 2 animals did not return in 3 months. Errors were markedly increased 1-2 weeks post-treatment in 4/5 subjects. Response rates increased for 2 animals within a week of TMT treatment and remained elevated for 5 weeks. Sustained rate increases occurred for 2 other animals 4-5 weeks after treatment. Thus, TMT effects on various aspects of incremental repeated acquisition behavior follow different time-courses.

Animals↗
PubMedDate not supplied

Transplacental pharmacokinetics and maternal/fetal plasma concentrations of cocaine in pregnant macaques near term.

The transplacental pharmacokinetics of cocaine were studied in three pregnant rhesus monkeys (Macaca mulatta) at 150-154 days of pregnancy (term approximately 165 days). Animals were dosed intramuscularly with cocaine hydrochloride at 1 mg/kg, supplemented with a tritiated cocaine tracer. Plasma cocaine and its metabolite benzoylecgonine levels were determined after separation by HPLC and subsequent quantification by liquid scintillation spectrometry. Cocaine levels peaked in maternal blood within 10-20 min after dosing, and cocaine was detected in fetal blood within 5 min, reaching peak concentrations within 30-120 min. Mean maternal elimination half-lives (t1/2) for cocaine and benzoylecgonine were 1.2 +/- 0.5 hr and 12.4 +/- 6.6 hr (+/- SEM), respectively; fetal half-lives were 0.5 +/- 0.2 and 7.7 +/- 3.0 hr. Mean maternal residence times were 1.9 +/- 0.5 and 17.0 +/- 9.1 hr for cocaine and benzoylecgonine, respectively; fetal values were 2.1 +/- 0.2 and 11.6 +/- 3.5 hr. Total areas under the concentration versus time curves (AUCs) for cocaine and benzoylecgonine in maternal plasma were 360 +/- 38 and 585 +/- 260 (ng/ml) hr, respectively; fetal values were 104 +/- 29 and 262 +/- 61 (ng/ml) hr. Based on AUC comparisons for cocaine, fetal exposures are thus approximately one-third of maternal exposures, demonstrating that substantial exposure to cocaine does occur in utero.

Acid-Base Equilibrium↗