Timing and space usage are disrupted by amphetamine in rats maintained on DRL 24-s and DRL 72-s schedules of reinforcement

RATIONALE: A differential-reinforcement-of-low-rate schedule (DRL) delivers reinforcement only when the interresponse time (IRT) exceeds a fixed time interval, thereby shaping rats to discriminate the timing of their responses. However, little is known about the motor behavior and location of the rats in the chamber during the IRTs that lead to reinforcement. Although amphetamine is known to disrupt DRL timing behavior, the effects of this drug on non-operant motor behavior during DRL performance has not yet been quantified. OBJECTIVE: The purpose of this research was to measure the motor behavior (movement trajectories in the horizontal plane and spatial location in the plane) during longer IRT’s after either vehicle or amphetamine treatment. METHOD: Experimental chambers were constructed with a force-plate actometer as the floor, and while performing the operant task, the rats’ motor behaviors were measured continuously with high temporal and spatial resolution. Separate groups of 8 male Sprague Dawley rats were maintained on either DRL 24-s or DRL 72-s schedules of water reinforcement in 4-hr recording sessions. RESULTS: Analyses of IRT distributions showed that the rats’ timing behavior conformed to their respective DRL requirements. In the absence of drug, analysis of motor behavior in pre-reinforcement intervals showed that rats located themselves away from the operandum, and exhibited very low levels of movement. Rats exhibited a significant temporal diminution of horizontal movement that reached a minimum 4–8 s before the rats moved to the operandum to execute operant responses. Amphetamine treatment increased locomotion, abolished the temporal movement gradient, and brought the rats closer to the operandum compared to vehicle treatment. Movement changes induced by amphetamine were accompanied by degraded timing behavior. CONCLUSIONS: Taken together, the data show that DRL training induced rats to locate themselves away from the operandum and to remain nearly motionless during longer IRTs, and that amphetamine treatment interfered with this complex of behavioral features

Relative bioavailability of calcium from calcium formate, calcium citrate, and calcium carbonate

Final publisher version is available online openly at: http://jpet.aspetjournals.org/content/313/3/1217.full.pdf Author accepted manuscript is available in compliance with NIH requirements at, http://jpet.aspetjournals.org/content/early/2005/02/25/jpet.104.081893/. Abstract is posted in fulfillment of the KU faculty's Open Access policy.Published Abstract: Calcium is an essential nutrient required in substantial amounts, but many diets are deficient in calcium making supplementation necessary or desirable. The objective of this study was to compare the oral bioavailability of calcium from calcium formate, a new experimental dietary calcium supplement, to that of calcium citrate and calcium carbonate. In a four-way crossover study, either a placebo or 1200 mg of calcium as calcium carbonate, calcium citrate, or calcium formate were administered orally to 14 healthy adult female volunteers who had fasted overnight. After calcium carbonate, the maximum rise in serum calcium (~4%) and the fall in serum intact para-thyroid hormone 1–84 (iPTH) (~20–40%) did not differ significantly from placebo. After calcium citrate, the changes were modestly but significantly (p < 0.05) greater, but only at 135 to 270 min after ingestion. In contrast, within 60 min after calcium formate serum calcium rose by approximately 15% and serum iPTH fell by 70%. The mean increment in area under the plasma concentration-time curve (0–270 min) for serum calcium after calcium formate (378 mg∙min/dl) was double that for calcium citrate (178 mg∙min/dl; p < 0.01), whereas the latter was only modestly greater than either placebo (107; p < 0.05) or calcium carbonate (91; p < 0.05). In this study, calcium formate was clearly superior to both calcium carbonate and calcium citrate in ability to deliver calcium to the bloodstream after oral administration. Calcium formate may offer significant advantages as a dietary calcium supplement

The Equilibrium Distribution of Gas Molecules Adsorbed on an Active Surface

We evaluate the exact equilibrium distribution of gas molecules adsorbed on an active surface with an infinite number of attachment sites. Our result is a Poisson distribution having mean $X = {\mu P P_s \over P_e}$, with $\mu$ the mean gas density, $P_s$ the sticking probability, $P_e$ the evaporation probability in a time interval $\tau$, and $P$ Smoluchowski's exit probability in time interval $\tau$ for the surface in question. We then solve for the case of a finite number of attachment sites using the mean field approximation, recovering in this case the Langmuir isotherm.Comment: 14 pages done in late

Absorption and elimination of formate following oral administration of calcium formate in female human subjects

Final publisher version is available online openly at: http://dmd.aspetjournals.org/content/33/2/282.full.pdf. Author accepted manuscript is available in compliance with NIH requirements at, http://dmd.aspetjournals.org/content/early/2004/11/16/dmd.104.001289. Abstract is posted in fulfillment of the KU faculty's Open Access policy.Published abstract: Calcium formate is a water-soluble salt of an essential mineral nutrient with potential for use as a dietary calcium supplement. Formate ion is a product of endogenous and xenobiotic metabolism, but sustained high plasma formate concentrations (such as occur in cases of methanol poisoning) are toxic to the retina and optic nerve. Humans and primates have reduced capacity for formate oxidation compared with rodents and dogs and are thus more sensitive to methanol (and formate) intoxication. To assess the potential for accumulation of formate ion upon repeated administration of calcium formate as a potential dietary calcium supplement, we measured plasma concentrations of formate in 14 adult human subjects before and after oral administration of a single large dose of calcium formate (3900 mg; ca. 3–6 times the anticipated dose for calcium supplementation). Plasma formate concentrations increased briskly from 0.024 ± 0.008 mM (endogenous formate) to reach Cmax (0.50 ± 0.04 mM) at 60 min postdose and then declined with a half-life of 59 ± 7 min. By 225 min postdose, plasma formate concentration had returned to baseline. With such a short half-life, repeated use of calcium formate as a dietary supplement, even three times daily, should not lead to progressive accumulation of formate. These findings are discussed in light of the production of formate by endogenous and xenobiotic metabolism and the kinetics of formate during methanol poisoning

Bone marrow transplantation alters the tremor phenotype in the murine model of globoid-cell leukodystrophy

Tremor is a prominent phenotype of the twitcher mouse, an authentic genetic model of Globoid-Cell Leukodystrophy (GLD, Krabbe’s disease). In the current study, the tremor was quantified using a force-plate actometer designed to accommodate low-weight mice. The actometer records the force oscillations caused by a mouse’s movements, and the rhythmic structure of the force variations can be revealed. Results showed that twitcher mice had significantly increased power across a broad band of higher frequencies compared to wildtype mice. Bone marrow transplantation (BMT), the only available therapy for GLD, worsened the tremor in the twitcher mice and induced a measureable alteration of movement phenotype in the wildtype mice. These data highlight the damaging effects of conditioning radiation and BMT in the neonatal period. The behavioral methodology used herein provides a quantitative approach for assessing the efficacy of potential therapeutic interventions for Krabbe’s disease

Demonstration of functional coupling between dopamine synthesis and its packaging into synaptic vesicles

This is the publisher's version, also available electronically from "http://link.springer.com".We have previously shown that the membrane-associated form of the GABA-synthesizing enzyme, glutamate decarboxylase 65 (GAD65), is activated by synaptic vesicle proton gradient-mediated protein phosphorylation. We now report that the rate-limiting enzyme in dopamine (DA) biosynthesis, tyrosine hydroxylase (TH), is regulated similarly to GAD65. The membrane-associated form of TH (MTH) was activated by conditions favoring protein phosphorylation (e.g. ATP) and was inhibited by phosphatase (e.g. calf intestine phosphatase). Furthermore, the ATP-mediated activation of MTH was abolished by conditions that disrupted the proton gradient of synaptic vesicles, e.g. the presence of carbonyl cyanidem-chorophenylhydrazone, gramicidin, or the V-type ATPase inhibitor (bafilomycin), but not the P-type ATPase inhibitor (vanadate). Moreover, DA newly synthesized from tyrosine by MTH and membrane-associated aromatic amino acid decarboxylase was taken up preferentially rather than pre-existing DA. Therefore, the previously proposed model showing close coupling between GABA synthesis and GABA packaging into synaptic vesicles by vesicular GABA transporters is also applicable to the DA system. Hence, it is concluded that there is a general coupling mechanism between neurotransmitter synthesis and packaging of transmitter into synaptic vesicles

Attraction of Adult Chironomidae (Diptera) to Incandescent Light Under Laboratory Conditions

The attraction of three chironomid species, Glyptotendipes paripes Edwards, Chironomus crassicaudatus Malloch, and Polypedilum halterale (Coquillett), to incandescent light of different colors and wattages was studied. Field-captured adults were released from the center of a dark room (9 by 9 m) equipped with a New Jersey light trap in each corner. The effects of color were determined by using 100-W lamps of red, orange, yellow, green, blue, and white. The effects of light intensity were studied by using 100, 60, 40, and 25-W white lamps. Measurements of light intensity of each lamp were taken. Among the colors tested in two separate combinations, white light attracted the maximum numbers of adults and red light the least. The three species exhibited a similar behavior. Among white light of different intensities, the maximum attraction of G. paripes occurred toward the highest intensity and the minimum toward the lowest intensity. The midge species responded more to the quantity (power or intensity) than to the quality (color or wavelength) of ligh

Striatal expression of a calmodulin fragment improved motor function, weight loss and neuropathology in the R6/2 mouse model of Huntington's disease

This is the published version, also available here: http://dx.doi.org/10.1523/JNEUROSCI.3307-09.2009.Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, caused by a polyglutamine expansion in the huntingtin protein (htt). Increasing evidence suggests that transglutaminase (TGase) plays a critical role in the pathophysiology of HD possibly by stabilizing monomeric, polymeric and aggregated htt. We previously reported that in HEK293 and SH-SY5Y cells expression of a calmodulin (CaM)-fragment, consisting of amino acids 76-121 of CaM, decreased binding of CaM to mutant htt, TGase-modified htt and cytotoxicity associated with mutant htt and normalized intracellular calcium release. In this study, an adeno-associated virus (AAV) that expresses the CaM-fragment was injected into the striatum of HD transgenic R6/2 mice. The CaM-fragment significantly reduced body weight loss and improved motor function as indicated by improved rotarod performance, longer stride length, lower stride frequency, fewer low mobility bouts and longer travel distance than HD controls. A small but insignificant increase in survival was observed in R6/2 mice with CaM-fragment expression. Immunoprecipitation studies show that expression of the CaM-fragment reduced TGase-modified htt in the striatum of R6/2 mice. The percentage of htt-positive nuclei and the size of intranuclear htt aggregates were reduced by the CaM-fragment without striatal volume changes. The effects of CaM-fragment appear to be selective, as activity of another CaM-dependent enzyme, CaM-dependent kinase II, was not altered. Moreover, inhibition of TGase-modified htt was substrate-specific since overall TGase activity in the striatum was not altered by treatment with the CaM-fragment. Together, these results suggest that disrupting CaM–htt interaction may provide a new therapeutic strategy for HD