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Biomedical subjects

S Swindell

Publications and source records attributed to S Swindell.

6 recordsLinked to original sources

Repeated formaldehyde effects in an animal model for multiple chemical sensitivity.

Chemical intolerance is a phenomenon observed in multiple chemical sensitivity (MCS) syndrome, an ill-defined disorder in humans attributed to exposure to volatile organic compounds. Amplification of symptoms in individuals with MCS resembles the phenomenon of psychostimulant- and stress-induced sensitization in rodents. We have recently tested in rats the hypothesis that repeated chemical exposure produces sensitization of central nervous system (CNS) circuitry. A rat model of MCS in our laboratory has employed several endpoints of CNS function after repeated formaldehyde (Form) exposure (1 h/day x 5 days/week x 4 weeks). Repeated Form exposure produced behavioral sensitization to later cocaine injection, suggesting altered dopaminergic sensitivity in mesolimbic pathways. Rats given repeated Form also demonstrated increased fear conditioning to odor paired with footshock, implicating amplification of neural circuitry guiding fear responding to a conditioned odor cue. Recent studies examining the effects of repeated Form on locomotor activity during each daily exposure showed a decrease in rearing activity after 12-15 days of Form exposure compared to air-exposed controls. EEG recordings taken 1 week after withdrawal from daily Form revealed altered sleep architecture. Some of the differences in sleep disappeared after subsequent brief (15 min) challenge with Form the next day. Overall, the findings indicate that repeated low-level chemical exposure produces behavioral changes that may be akin to those observed in individuals with MCS, such as greater sensitivity to chemicals manifest as increased anxiety upon chemical exposure and altered sleep and/or fatigue. Study of the underlying CNS changes will provide a basis for mechanistically based animal models for MCS.

Animals↗

Behavioral economics and within-session changes in responding.

Pigeons and rats responded on fixed-ratio schedules with requirements ranging from 5 to 120 responses. Consistent with past results from several schedules and procedures, responding usually changed systematically within experimental sessions. The within-session changes were usually larger and were less symmetrical around the middle of the session for schedules that provided higher, rather than lower, rates of reinforcement. These results suggest that similar variables contribute to within-session changes in responding under different schedules. When an economic demand function was fit to the data, the intensity and elasticity of demand for food and the percentage of the variance accounted for decreased within sessions, although the trend for elasticity did not reach statistical significance for pigeons. These results suggest that relatively short sessions should be used to study economic demand in open economies and that demand may differ at different times in a session and in sessions of different lengths. Within-session changes in intensity, but not necessarily elasticity, of demand are consistent with behavioral economic theories.

Animals↗

Within-Session Changes in Adjunctive and Instrumental Responding

Rats pressed levers for food delivered by several fixed interval schedules. A drinking spout or running wheel was also available during some conditions, but not during others. The rate of lever pressing, drinking and running often changed within experimental sessions. The within-session patterns of lever pressing did not differ when drinking or running was available and when it was not. The correlation between the amount of lever pressing and the amount of drinking or running at a particular time in the session was inconsistently positive or negative. Finding within-session changes in responding for adjunctive behaviors implies that the factors that produce these changes are present for both adjunctive and instrumental behavior. Finding inconsistent correlations between instrumental responding and adjunctive behaviors questions arousal and interference from adjunctive behaviors as explanations for within-session changes in instrumental responding.

Journal Article↗

Within-session changes in responding during concurrent schedules with different reinforcers in the components.

Rats and pigeons responded on several concurrent schedules that provided different reinforcers in the two components (food and water for rats, Experiment 1; wheat and mixed grain for pigeons, Experiment 2). The rate of responding and the time spent responding on each component usually changed within the session. The within-session changes in response rates and time spent responding usually followed different patterns for the two components of a concurrent schedule. For most subjects, the bias and sensitivity to reinforcement parameters of the generalized matching law, as well as the percentage of the variance accounted for, decreased within the session. Negative sensitivity parameters were sometimes found late in the session for the concurrent food-water schedules. These results imply that within-session changes in responding could cause problems for assessing the validity of quantitative theories of concurrent-schedule responding when the components provide different reinforcers. They question changes in a general motivational state, such as arousal, as a complete explanation for within-session changes in responding. The results are compatible with satiation for, or sensitization-habituation to, the reinforcers as explanations.

Animals↗

Molecular rearrangement of lactose plasmid DNA associated with high-frequency transfer and cell aggregation in Lactococcus lactis 712.

High-frequency conjugation of the lactose plasmid pLP712 is associated with a constitutive cell aggregation phenotype and is facilitated by cointegration with a sex factor. Analysis of 23 independently derived enlarged lactose plasmids revealed that the sex factor DNA present in cointegrates varied in size. This suggested that more than simple cointegration with a sex factor plasmid was involved. Further analysis led to the discovery of a chromosomally located sex factor that could excise and be lost or exist as labile plasmid DNA. Cointegration with this sex factor was shown to be promoted by transposition of a copy of ISSI present on the lactose plasmid, and models are presented to account for the complex and variable structures of the resulting enlarged lactose plasmids.

Base Sequence↗

Nisin biosynthesis genes are encoded by a novel conjugative transposon.

Genes for biosynthesis of the lactococcal peptide antibiotic nisin were shown to be encoded by a novel chromosomally located transposon Tn5301. The element is 70 kb in size and lacks inverted repeats at its termini. Although a copy of the insertion sequence IS904 is located near to one end, this did not appear to be involved in the transposition process. The integrated element is flanked by the directly repeated sequence 5'-TTTTTG-3'. Analysis of ten independent transconjugants revealed that Tn5301 integration is site-specific; two chromosomal targets were identified and shown to have some sequence homology. The element shares features with the Tn916 family of conjugative transposons and with Tn554 but is also exhibits some unique properties. Tn5301 is thus considered to be the prototype of a novel class of conjugative transposon.

Base Sequence↗