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M A Bixler

Publications and source records attributed to M A Bixler.

5 recordsLinked to original sources
PubMed1996

Comparison of the effects of typical and atypical anxiolytics on learning in monkeys and rats.

Atypical anxiolytics such buspirone have been reported to produce fewer disruptive effects on complex behaviors than some typical anxiolytics from the benzodiazepine class. To extend this analysis, several drugs from both drug classes were directly compared in two species (rhesus monkeys and rats) using a repeated-acquisition procedure. In monkeys responding under a multiple schedule of reinforcement consisting of acquisition (learning) and performance components, buspirone (0.032-0.52 mg/kg), 8-hydroxy-dipropylaminotetralin (8-OH-DPAT;0.032-0-56 mg/kg), chlordiazepoxide (CDZP; 1-56 mg/kg) and alprazolam (0.032-0.32 mg/kg) produced dose-dependent decreases in overall response rate in all subjects. However, with buspirone and 8-OH-DPAT, these rate-decreasing effects occurred in acquisition at lower doses than in performance. The effects on overall accuracy (i.e., percent errors) in monkeys were variable across drugs and drug classes. Both 8-OH-DPAT and alprazolam produced large increases in percent errors in acquisition at doses that had little or no effect on errors in performance. Buspirone also had differential effects on percent errors across components, but the error-increasing effects in acquisition were smaller. CDZP administered either orally or intramuscularly produced only small increases in errors, and these occurred at doses that substantially decreased the overall rate of responding in both components of the multiple schedule. In rats responding under a repeated-acquisition procedure, buspirone (1-5.6 mg/kg), 8-OH-DPAT (0.056-3.2 mg/kg) and CDZP (1.8-32 mg/kg) produced dose-dependent decreases in overall response rate. Similar to acquisition data in monkeys, buspirone and 8-OH-DPAT also increased percent errors to a greater extent than CDZP. These data indicate that learning is sensitive to disruption by drugs with 5-HT1A agonist properties, and that atypical anxiolytics with 5-HT1A agonist properties are no less disruptive to "cognitive" processes than typical anxiolytics such as the benzodiazepine alprazolam.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Differential effects of ionizing radiation on the acquisition and performance of response sequences in rats.

To compare the effects of ionizing radiation on the acquisition and performance of response sequences, rats responding under a multiple schedule of food reinforcement were each administered 0.5-6 Gy of 60Co gamma radiation. In one component of the multiple schedule, subjects acquired a different three-response sequence each session by responding sequentially on one of three response keys in the presence of three consecutively presented colors (repeated acquisition). In the other component, the three-response sequence was the same each session (performance). The response sequence in each component was maintained by food presentation under a second-order fixed-ratio (FR) 2 schedule. Errors in both components produced a 5-sec timeout but did not reset the sequence. In all subjects, 0.5-6 Gy of gamma radiation dose-dependently decreased response rates in both components for 1-5 days postexposure. These gamma-ray doses also produced dose-dependent increases in errors in both components, but only at doses that substantially decreased response rate. Unlike the effects on response rate in both components, which were comparable over the 5-day period after exposure, the effects on accuracy were generally different for the two components. More specifically, the largest increases in percent errors in the performance component occurred on day 2 postexposure, whereas the largest increases in percent errors in the acquisition component occurred on day 4 postexposure. Taken together, these results indicate that (1) acute sublethal doses of gamma radiation differentially affect the acquisition and performance of response sequences, (2) these doses of gamma radiation differentially affect the measures of rate and accuracy within each condition of behavior, and (3) using a sensitive baseline, which includes an accuracy measure, provides important information about the disruptive effects of radiation that could not be predicted from the effects on response rate alone.

Animals↗
PubMed1994

Effects of chlordiazepoxide, 8-OH-DPAT and ondansetron on radiation-induced decreases in food intake in rats.

Studies of radiation effects on performance are often complicated by concurrent radiation-induced decreases in feeding behavior (i.e., "anorexia"). To evaluate the pharmacological specificity of these decreases in food intake, the interactions of radiation with three prototypical drugs were studied. Single daily i.p. administration of a dose of chlordiazepoxide, ondansetron or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was given to groups of rats for 5 days after either a single nonlethal 4.5-Gy dose of ionizing radiation (bremsstrahlung or gamma rays) or a sham exposure. The food intake for each group was measured 60 min and 24 hr after food presentation. Radiation alone significantly decreased food intake during the 60-min test on each treatment day and for the 5-day period when data were averaged. Chlordiazepoxide (1.8-18 mg/kg) and 8-OH-DPAT (0.1-1 mg/kg) produced significant dose-dependent increases in food intake during the 60-min test in both irradiated and sham-irradiated groups, whereas ondansetron (0.1-1 mg/kg) did not alter food intake at any dose tested. The dose effects at 60 min were significant on each treatment day for chlordiazepoxide, on 4 of 5 days for 8-OH-DPAT and for both drugs when data for all 5 days were combined. In no case, however, was a significant interaction obtained for radiation and any dose of the three drugs. After 24 hr, decreases in intake were obtained in a few subjects in 3 of 12 total radiation groups. These results suggest that radiation-induced decreases in food intake do not result from damage to the mechanisms by which chlordiazepoxide and 8-OH-DPAT increase food intake and that hyperphagic agents from these two different classes may have therapeutic value for attenuating radiation-induced anorexia.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Seizures decrease regional enzymatic hydrolysis of N-acetyl-aspartylglutamate in rat brain.

Previous results have shown that kindled seizures increase N-acetyl-aspartylglutamate (NAAG) levels in the entorhinal cortex, while non-kindled convulsions have no effect. To further explore possible relationships between epilepsy and the physiology of NAAG, the effect of amygdaloid kindling on the activity of a NAAG-hydrolyzing enzyme was examined in specific brain regions associated with limbic seizures. NAAG is hydrolyzed into glutamate (Glu) and N-acetyl-aspartate (NAA) by N-acetylated-alpha-linked acidic dipeptidase (NAALADase), a membrane-bound peptidase. We found that convulsions decreased NAALADase activity and these effects were generalized to several brain regions. While small decreases in the hippocampus were specific to kindling, the decreases in other limbic regions were larger, non-specific, and appear to be aftereffects of convulsions; i.e. not specific to kindling. Although there is evidence that NAAG may be an excitatory neurotransmitter, it could also function as a storage form of Glu. Thus, a reduction in NAALADase activity could reduce the availability of Glu at certain synapses, which might be a homeostatic mechanism for lessening susceptibility to further seizures.

Animals↗