Effects of dopamine receptor blockade on avoidance performance: assessment of effects on cue-shock and response-outcome associations.
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Biomedical subjects
Publications and source records attributed to J Irwin.
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DNA damage and repair was assayed by the loss and restoration of DNA supercoiling in nucleoids. This technique was used to assess the effects of inhibition of (ADP-ribose)n biosynthesis by 3-aminobenzamide on the capacity to repair DNA of mouse leukaemia L1210 cells following damage by gamma-irradiation and by the monofunctional alkylating agent, dimethyl sulphate. 3-Aminobenzamide partially inhibits restoration of supercoiling following gamma-irradiation and dimethyl sulphate treatment, but inhibits neither the enzymic incision events leading to breaks in the DNA nor the repair synthesis. This inhibition of repair can be observed at very low doses of damaging agents. These observations confirm and extend the evidence that (ADP-ribose)n biosynthesis is required for efficient cellular recovery from DNA damage. In particular, the nucleoid technique permits the demonstration that 3-aminobenzamide inhibits DNA repair after gamma-radiation; it is not possible to draw this unequivocal conclusion with the data from alkaline sucrose gradients because this technique is too insensitive. 1-beta-D-Arabinofuranosylcytosine, which inhibits semiconservative DNA replication, also retards repair, and this effect can be reversed by the addition of deoxycytidine. The inhibitors of DNA excision repair, arabinosylcytosine, hydroxyurea or 3-aminobenzoamide increase the steady-state number of DNA breaks. Thus, they can be used to enhance even further the sensitivity of the nucleoid assay of repair.
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A circulating factor capable of inducing symptoms of dysmenorrhea has been demonstrated in 10 women by collecting plasma during periods of dysmenorrhea and infusing it during asymptomatic intervals. Typical symptoms of abdominal pain occurred in 8 of 12 women who received a plasma infusion that had been drawn at the time symptoms were present. Plasma drawn at the time of no symptoms, when given to 10 women, produced no abdominal pain (P less than .01). Combinations of pain and/or emotional irritability were found in 11 of 12 women after symptomatic units were infused and in only 2 of 10 women after asymptomatic units were infused (P less than .001). The uterus need not be involved, as 7 of 10 patients had a hysterectomy prior to the infusions. It is suggested that a circulating factor may activate prostaglandin synthesis, which in turn may stimulate the neuronal system, thus causing symptoms.
Hydroxyurea inhibition is a convenient method of suppressing replicative DNA synthesis for DNA excision-repair measurement by the BND cellulose technique. Nonetheless, hydroxyurea can introduce artefacts by direct reaction with repair-inducing compounds and by long-term inhibition of the overall repair process. A simple technique of overcoming these problems is described. Cells are reacted with repair-inducing compounds in the absence of hydroxyurea, the cells are washed free of inducer, hydroxyurea is added to 2 mM, and after a short period to establish replication inhibition, 3H dThd is added and repair measured over a one-hour incubation period.
The effects of inescapable shock on subsequent T-maze water escape and position discrimination performance were evaluated in seven experiments. Escapable shock did not disrupt water escape performance; however, escape performance was retarded 24 hr after inescapable shock. These deficits were not apparent if escape was possible upon stress inception; however, pronounced deficits were noted if sustained active responding was necessitated by briefly (3-5 sec) preventing escape. When water escape testing was conducted in relatively warm water (20 degrees C), the disruptive effects of preshock were not apparent. In colder water (15 degrees C), which increases the motor difficulty of the task, the disruptive effects of preshock were noted. When the motor difficulty of the task was increased further, by testing mice in 10 degrees C water, or when the associative difficulty was increased by using a vigorous reversal learning task, the differences between the preshocked and nonpreshocked groups were obviated. Exposure to inescapable shock did not disrupt position discrimination performance regardless of the motor difficulties of the task. Similarly, deficits of discrimination performance were not apparant in mice exposed to inescapable shock even when the associative difficulty of the task was increased by removing intramaze cues or by testing animals in a position discrimination reversal task. It is concluded that inescapable shock results in deficits of response maintenance but probably has a minor, if any, influence on cognitive/associative processes.
Following exposure to inescapable shock, mice exhibit deficits of escape performance, which are progressively more pronounced as training continues. Comparable effects were produced by DA and NE depletion by alpha-MpT and reserpine, NE depletion by FLA-63, and DA receptor blockade through haloperidol. Treatment with PCPA or 5-HTP did not influence performance. The disruptive effects of reserpine and alpha-MpT, as well as haloperidol and FLA-63, were additive. Unexpectedly, mice that received both reserpine and FLA-63 exhibited escape latencies that were significantly lower than those of mice that received either treatment alone. Consistent with the view that increased DA synthesis in the reserpine plus FLA-63 condition prevented the escape interference, L-DOPA antagonized the effects of both alpha-MpT and FLA-63. The results suggest that DA and NE act in a serial fashion to produce the escape deficits. Moreover, although both newly synthesized and previously stored amines contribute to the interference, the short latency responses seen during initial test trials could not be ascribed to previously stored amines.
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The effects of inescapable shock on subsequent escape performance and shock-elicited activity were examined in six lines of mice selectively bred for differences in general locomotor activity. The line differences in locomotor activity were found to be unrelated to the differences observed on shock-elicited activity. However, escape performance following exposure to inescapable shock was predictable from the levels of shock-elicited activity. Those lines that displayed the greatest decline in motor activity during shock likewise displayed the most pronounced escape deficits. The line differences in escape performance induced by inescapable shock could be mimicked by treatment with a tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine. As predicted, the lines that displayed the least interference after tyrosine hydroxylase inhibition exhibited the smallest reduction in levels of catecholamines. The effects on escape performance following inescapable shock are interpreted in terms of the role of response maintenance deficits produced by catecholamine depletion.
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An assessment of risk in handling microbial agents at a major biomedical research institute is given. Included also are the risks associated with handling tissue cultures and animals. Two computer programs are described for the storage and retrieval of data on agents, tissue cultures, and animals.
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