Browsing by Subject "locomotor activity"

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    Core Body Temperature Regulation and Locomotor Activity
    (Office of the Vice Chancellor for Research, 2014-04-11) Yoo, Yeonjoo; Kelley, Maire; Zaretsky, Dmitry; Molkov, Yaroslav
    Methamphetamine (Meth) enhances locomotor activity, and is known to cause life-threatening hyperthermia. There has been much debate about whether the locomotion plays a major role in hyperthermia caused by Meth or other stimulants. The existing model of the neural circuitry putatively involved in this phenomenon [1] accurately reproduces the temperature response to the different doses of Meth. We compared locomotor activity observed in the same experiments with activation patterns of neuronal populations as predicted by the model. We found that time-courses of locomotor activity closely resembles the activity of one particular node in the model putatively representing the medullary level. However, the data on locomotion did not match the model in the initial phase of the response within 1 hour after the injection. Therefore, we hypothesized that there were some changes in thermogenesis and heat exchange mechanisms that largely control temperature response during the first hour and make the influence of locomotion relatively small. The objective of the study was to measure the temperature dynamics in rats running on a treadmill at different speeds and to construct a mathematical model explaining the mechanism of their core body temperature response to such an intervention that takes into account potential changes in heat exchange, sensory input and feedback control mechanisms. In the experiments for every speed of 0, 6, 12, and 18 m/min we had 4 rats running for 15 min. For each speed we averaged the temperature over 4 rats to get the average temperature response curve. First, we found that the temperature response curves for different treadmill speeds were not different statistically. Second, every response curve starts with a short but profound (~0.25 deg C in the first 5 min) drop in the body temperature followed by virtually linear rise of the temperature which significantly (by ~1 deg C) overshoots the baseline temperature. To explain these findings we set up a model in a form of a system of two differential equations that described the change in the body temperature and the change in the body heat production under the hypothesis that there are contributions of varying heat exchange, sensory input and feedback mechanisms in thermogenesis. All parameters in the system were subject to fitting experimental time series of temperature response of rats to 4 consistent speeds of 0, 6, 12, and 18 m/min on treadmills. We found, that a sudden drop of the body temperature below the baseline in the first five minutes after rats were removed from their cages and placed on a treadmill was a result of the increased heat dissipation caused by changes in the body position and movement of rats. The following fast recovery of the body temperatures to the normal level was provided by the feedback mechanisms activated by the temperature drop and changed sensory input. Meth continues to stimulate thermogenesis even after the baseline temperature is achieved from feedback mechanisms. Estimated contribution of the locomotion was negligible as compared to the latter and hence played a relatively small role in the temperature change. We predict that varying locomotion might manifest itself in temperature dynamics after much longer (~1 hour) exposure to running. The suggested system, which considers major factors defining body temperature response, can help to uncover the mechanisms of hyperthermia elicited by Meth, but also can be used to understand the thermoregulatory mechanisms which underlie the responses to simultaneous changes in environmental and physical conditions.
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    Multivariate Concentric Square Field unveils behavioral exploratory categories of locomotor activity in mouse model of Down syndrome
    (Office of the Vice Chancellor for Research, 2015-04-17) Stancombe, Kailey E.; Goodlett, Charles R.; Stewart, Robert J.; Stringer, Megan; Roper, Randall J.
    Down Syndrome (DS), trisomy 21(Ts21), is a genetic condition in which a third copy of chromosome 21 is present, and results in neurodevelopmental deficits including intellectual disability. DS has been modeled in mice; Ts65Dn mouse model displays many of the phenotypes associated with DS, including cognitive deficits. We previously studied behavioral phenotypes of Ts65Dn mice and observed significantly increased locomotor activity in a novel arena (an “open field”). In those studies, treatment of the Ts65Dn mice with ~10 mg/kg/day of epigallocatechin-3-gallate (EGCG), a selective inhibitor of the DYRK1A kinase (one of the genes implicated in the neurodevelopmental deficits in DS and in Ts65Dn mice), failed to attenuate hyperactivity. Locomotor activity in an open field is a basic measure of general exploration in a simple environment, and was only moderately sensitive to the hyperactivity of the Ts65Dn mice. The aim of the current study was to use a more advanced analysis of behavioral patterns of exploration in a more complex, multi-partitioned arena, termed the Multivariate Concentric Square Field (MCSF). The advantage of MCSF is that it provides more elaborate measures of exploratory behavior by examining different categories of exploration: general activity, exploratory activity, risk assessment, risk taking and shelter seeking behavior. Trisomic mice and euploid littermates were treated with a continuous high dose (~100 mg/kg/day) of EGCG or water (controls) beginning at weaning. At seven weeks of age, they were tested in the MCSF on two consecutive days. Our current results indicate that Ts65Dn mice displayed more exploratory behavior compared to controls, and the EGCG treatment may have normalized exploratory behavior toward that of controls. Identifying altered patterns of exploratory behavior in the Ts65Dn mouse and the normalizing effects of EGCG treatment may help provide a therapeutic approach to DS.
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    Selective breeding for high alcohol consumption and response to nicotine: locomotor activity, dopaminergic in the mesolimbic system, and innate genetic differences in male and female alcohol-preferring, non-preferring, and replicate lines of high-alcohol drinking and low-alcohol drinking rats
    (Springer, 2018-09) Deehan, Gerald A., Jr.; Hauser, Sheketha R.; Getachew, Bruk; Waeiss, R. Aaron; Engleman, Eric A.; Knight, Christopher P.; McBride, William J.; Truitt, William A.; Bell, Richard L.; Rodd, Zachary A.; Psychiatry, School of Medicine
    Rationale There is evidence for a common genetic link between alcohol and nicotine dependence. Rodents selectively bred for high alcohol consumption/responsivity are also more likely to self-administer nicotine than controls. Objectives The experiments examined the response to systemic nicotine, the effects of nicotine within the drug reward pathway, and innate expression of nicotine-related genes in a brain region regulating drug reward/self-administration in multiple lines of rats selectively bred for high and low alcohol consumption. Methods The experiments examined the effects of systemic administration of nicotine on locomotor activity, the effects of nicotine administered directly into the (posterior ventral tegmental area; pVTA) on dopamine (DA) release in the nucleus accumbens shell (AcbSh), and innate mRNA levels of acetylcholine receptor genes in the pVTA were determined in 6 selectively bred high/low alcohol consuming and Wistar rat lines. Results The high alcohol-consuming rat lines had greater nicotine-induced locomotor activity compared to low alcohol-consuming rat lines. Microinjections of nicotine into the pVTA resulted in DA release in the AcbSh with the dose response curves for high alcohol-consuming rats shifted leftward and upward. Genetic analysis of the pVTA indicated P rats expressed higher levels of α2 and β4. Conclusion Selective breeding for high alcohol preference resulted in a genetically divergent behavioral and neurobiological sensitivity to nicotine. The observed behavioral and neurochemical differences between the rat lines would predict an increased likelihood of nicotine reinforcement. The data support the hypothesis of a common genetic basis for drug addiction and identifies potential receptor targets.