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Behavioral and neuropharmacological analysis of amphetamine and 2,5-dimethoxy-4-methylamphetamine in rats.

A comparison of the behavioral pharmacology of DOM and amphetamine in rats indicated that lower doses (0.10-1.0 mg/kg) of the two agents had similar effects on schedule-controlled food-reinforced and shock-avoidance behavior. Similarities were also noted in their effects on horizontally directed motor activity when testing was preceeded by a period of acclimation. However, most doses of DOM tended to decrease unacclimated motor activity, while amphetamine increased this behavior. Neuropharmacological antagonism studies indicated that brain catecholamines (CA) and serotonin (5-HT) are involved in the behavioral effects of both DOM and amphetamine. Cinanserin, a 5-HT receptor blocker, attenuated the behavioral disruptive effects of both agents on food-reinforced responding. Cinanserin attenuated the effects of all doses of DOM and those of higher doses of amphetamine on shock avoidance. When given prior to lower doses of amphetamine, there was a greater behavioral stimulation than when amphetamine was given alone. Prior depletion of brain CA with alpha-methyltyrosine (alpha-MT) did not affect DOM induced disruption of food-reinforced responding, while alpha-MT attenuated the behavioral effects of all doses of DOM and amphetamine on shock avoidance. These data suggest that DOM and amphetamine share a similar component in their mechanism of action which depends on the availability of a releasable pool of brain CA.

DOM 2,5-Dimethoxy-4-Methylamphetamine

Effect of R(-)2,5-dimethoxy-4-methylamphetamine on uterine and umbilical blood flow in conscious pregnant sheep.

Pregnant sheep and their fetuses were instrumented between 110 to 120 days of gestation (term, 145 days) for monitoring maternal and fetal arterial blood pressure, heart rate and blood flow in the maternal uterine and fetal intra-abdominal umbilical arteries. The administration of 2,5-dimethoxy-4-methylamphetamine (DOM, a 5-HT2 agonist) i.v. to the ewe in doses ranging from 1 to 20 micrograms/kg of ewe body weight produced dose-dependent decreases in the blood flow of the uterine and umbilical arteries. This was accompanied by an increase in the arterial blood pressure of the mother and fetus and a decrease in the fetal heart rate. DOM significantly increased the vascular resistance to blood flow in the uterine and umbilical arteries. The maximal increase in the vascular resistance of the uterine and umbilical arteries was 19.6- and 2.6-fold, respectively. Ketanserin, a 5-HT2 antagonist (1 mg/kg), administrated 30 min prior to DOM significantly inhibited the reduction in blood flow in the uterine and umbilical arteries to DOM and blocked the increased vascular resistance in these vessels. The inhibitory effects of ketanserin on the responses to DOM in the uterine and umbilical arteries were surmountable. Our results indicate that DOM is a potent constrictor of the uterine and umbilical vasculature which may lead to fetal distress as evidenced by a decrease in fetal heart rate and arterial blood PO2. 5-HT2 receptor stimulation by DOM may be involved in these effects since they were blocked by ketanserin.

DOM 2,5-Dimethoxy-4-Methylamphetamine

Ecological Restoration of the Soil-Like Function in the Bauxite Residue: Natural Microbiomes Mediated Molecular Transformation of Dissolved Organic Matter.

Soilization of bauxite residues offers a scalable route for long-term carbon management and ecological restoration. However, the microbial processes that transform exogenous organic inputs into stable soil-like carbon pools remain poorly resolved. Here, we combined cross-ecosystem meta-analysis, machine-learning prediction, native synthetic community (SynCom) construction, 13C-labeled straw microcosms, field validation, Fourier transform ion cyclotron resonance mass spectrometry, and genome-resolved metagenomics to unravel microbiome-mediated carbon transformation at the dissolved organic matter (DOM) molecular scale. Our meta-analysis revealed that alkaline industrial wastes retained soil-like DOM signatures but were enriched in microbial humic- and protein-like components, indicating active yet incomplete carbon processing. Guided by these patterns, native SynCom inoculation increased 13C incorporation into total organic carbon (TOC) and dissolved organic carbon (DOC), enlarged biodegradable and adsorbable DOC fractions, and shifted DOM from recalcitrant aromatic pools toward oxygenated carbohydrate-, tannin-, and phenolic-like molecular classes. Genome-resolved analyses linked this transformation to complementary polymer degradation and nutrient-cycling functions across fungal and bacterial guilds, including enriched carbohydrate-active enzymes in straw-carbon-utilizing metagenome-assembled genomes. Null model and thermodynamic analyses further showed that microbial communities were constrained by homogeneous selection, whereas DOM molecules were diversified through variable selection and redox-dependent transformation. Field-scale validation confirmed that SynCom promoted TOC and DOC accumulation and humic-like, high-density DOM fractions under alkaline conditions. Together, these findings establish a mechanistic framework in which functional microbiomes couple plant carbon depolymerization, DOM molecular diversification, and mineral-interactive carbon stabilization, providing a microbiome-guided strategy for carbon sequestration and soilization in the bauxite residue.

Soil

Delayed onset muscle soreness: mechanisms and management.

This review describes the phenomenon of delayed onset muscle soreness (DOMS), concentrating upon the types of muscle contraction most likely to produce DOMS and the theories underlying the physiological mechanisms of DOMS. Ways of attempting to reduce the effects of DOMS are also summarized, including the application of physical and pharmacological therapies to reduce the effects of DOMS and training for reduction or prevention of DOMS.

Connective Tissue

Ontogeny of the endogenous stimulatory rhythm regulating prolactin secretion in immature female rats.

PRL secretion in the female rat is regulated by an endogenous stimulatory rhythm (ESR). This rhythm consists of two components: a nocturnal (N) component whose activity is greatest by 0300 h and a diurnal (D) component that peaks at approximately 1700 h. This periodicity coincides with the periods of the N and D surges of PRL in responses to the mating stimulus. Furthermore, we have shown that the ESR is involved in the regulation of mating-induced PRL surges. Mating causes a lowering of dopaminergic tone which reveals the ESR for PRL. The ability of immature female rats to express PRL surges induced by copulomimetic stimuli begins at 25 days of age. In this study we investigated the ontogeny of the ESR in immature female rats in order to observe the relationship between the onset of PRL secretion induced by copulomimetic stimuli and the development of the ESR. Immature female rats were raised in our colony and kept with their dams until used in an experiment or weaned at 23 days of age where appropriate. At 15, 20, 23, 24, 25, or 30 days of age female rats received a single ip injection of domperidone (DOM; 5 mg/kg) or saline vehicle at 0300, 1200, or 1700 h. Thirty minutes after the injection the rats were decapitated, and trunk blood was collected. PRL was measured by RIA. DOM had no effect on PRL secretion as compared to that in saline-treated controls at 15 days of age. However, in all other age groups DOM induced a significant increase in PRL levels compared to those in saline-treated animals regardless of the time of injection. In addition, there was no time of day difference in the PRL secretory response to DOM in rats 15-23 days of age. However, rats treated with DOM at 0300 h at 24 days of age secreted approximately 2-fold greater PRL than rats treated similarly at 1200 or 1700 h. Moreover, at 25 and 30 days of age, rats treated with DOM at either 0300 or 1700 h secreted significantly greater PRL than rats treated similarly at 1200 h. These results suggest that the ESR for PRL secretion begins by 24 days of age. In addition, they indicate that the hypothalamic developmental event preceding and required for expression of mating-induced surges of PRL is the establishment of the ESR.

Aging

Receptor mechanisms for 5-hydroxytryptamine (5-HT) in isolated ovine umbilical vein.

5-Hydroxytryptamine (5-HT) and 2,5-dimethoxy-4-methyl-amphetamine (DOM) produced a concentration-dependent contraction in isolated umbilical veins obtained from fetal lambs within 2 weeks of term. Contractions to 5-HT were antagonized by ketanserin, mianserin and methiothepin with the dissociation constants (KB) being 2.17 +/- 0.36, 1.37 +/- 0.55 and 1.98 +/- 0.48 nM, respectively. The order of potency of serotonergic agonists in this tissue was: DOM greater than 5-HT greater than alpha-methyl-5-HT greater than 1(3-chlorophenyl) piperazine (mCPP) greater than m-trifluoromethyl-phenylpiperazine (TFMPP) greater than 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) = 2-methyl-5-HT. alpha-Methyl-5-HT was a full agonist compared to 5-HT. DOM possessed greater affinity but less efficacy than that of 5-HT. The affinities and efficacies of the other agonists studied were lower than those of 5-HT. Variation in the sensitivity and potency of agonists is primarily due to variations in their affinity for 5-HT receptors. Assessment of receptor occupancy vs. functional response demonstrated very little, if any, receptor reserve for 5-HT receptors in this tissue. Contractile responses to DOM, 8-OH-DPAT, mCPP and 2-methyl-5-HT were effectively blocked by ketanserin. The dissociation constants (KB) of ketanserin against these agonists were as follows: DOM, 2.78 +/- 0.85 nM; 8-OH-DPAT, 3.47 +/- 1.12 nM; mCPP, 1.45 +/- 0.51 nM; 2-methyl-5-HT, 1.99 +/- 0.74 nM. The dissociation constant of MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) vs. 5-HT was 13833 nM. No antagonism by prazosin (10(-7) M) or yohimbine (10(-7) M) of the responses to 5-HT was observed. These results indicate that 5-HT2 receptors are present in the ovine umbilical vein. 5-HT3 receptors were not present in this tissue. Activation of alpha-adrenoceptors was not involved in the contractions to 5-HT.

DOM 2,5-Dimethoxy-4-Methylamphetamine

Phenylalkylamine stimulants, hallucinogens, and designer drugs.

Phenylalkylamine derivatives produce several types of behavioral effects including central stimulation and hallucinogenic activity. SAR are being formulated and already (a) it has been demonstrated that each of these types of activities is associated with a distinct SAR, and (b) it is now possible to use these SAR to make predictions as to whether the stimulus effects of certain PAAs are primarily AMPH-like or DOM-like. The AMPH-like nature of PAAs seems to involve a dopaminergic mechanism whereas DOM-like activity involves a serotonergic (in particular a 5-HT2) mechanism. It is apparent, however, that there is an additional type of activity emerging from studies with some PAAs that is neither solely AMPH-like nor DOM-like. MDA seems to produce both types of actions and may even produce this third type of effect. MDMA produces AMPH-like and MDA-like effects, but does not produce DOM-like effects. Other agents, such as MDE and PMMA, produce neither AMPH-like nor DOM-like effects but clearly produce MDMA-like stimulus effects. Thus, there is a third type of SAR that may be formulated. In all likelihood, however, few PAAs will be shown to produce a single "pure" activity and because there are some similarities in the different SARs (even though there are some very clear differences) it is not unreasonable to assume that many PAAs will produce more than one type of effect or will display vestiges of one or more different components of action. Therefore, although a PAA may be classified as primarily producing one type of effect, it should be understood that the other types of effects are not necessarily absent.(ABSTRACT TRUNCATED AT 250 WORDS)

Aniline Compounds

Chemical and biological studies of 1-(2,5-dihydroxy-4-methylphenyl)-2-aminopropane, an analogue of 6-hydroxydopamine.

Autoxidation of the bis(O-demethyl)-p-hydroquinone metabolite of the psychotomimetic amine 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) at pH 7.4 leads exclusively to a bicyclic imino quinone. This imino quinone is a good alkylating agent, forming covalent adducts via 1,4 addition to thiols. The autoxidation appears to be dependent on trace metal catalysis and is dramatically inhibited by components of the 10000g supernatant fraction of rabbit liver homogenates. Incubation of tritium-labeled hydroquinone with bovine serum albumin under oxidizing conditions leads to significant amounts of nonextractable radioactivity which presumably is dependent on imino quinone alkylation of nucleophilic functionalities present on macromolecules. Incubation of tritium-labeled DOM with rabbit microsomes in the presence of NADPH leads to irreversible binding of the label to macromolecular components of the microsomes. Since this binding is NADPH dependent, it is likely that metabolic conversion of DOM to the hydroquinone is involved. The imino quinone oxidation product is highly lypophilic and is capable of crossing the blood-brain barrier. Intravenous administration of tritium-labeled imino quinone to rats resulted in significant nonextractable radioactivity in brain tissue. These properties of the hydroquinone metabolite parallel those reported for the structurally related sympatholytic compound 6-hydroxydopamine and have led to the hypothesis that the psychotomimetic properties of DOM may be mediated through 6-hydroxydopamine-type interactions of the hydroquinone with important macromolecules in the brain.

DOM 2,5-Dimethoxy-4-Methylamphetamine

5-HT2 receptor-stimulated calcium influx in ovine uterine artery in late pregnancy.

The effects of 5-hydroxytryptamine (5-HT) and 2,5-dimethoxy-4-methyl-amphetamine (DOM) on the Ca2+ influx in the ovine uterine artery in late pregnancy have been studied by measuring 45Ca2+ uptake. Both 5-HT and DOM (2.5 x 10(-8) M to 2.5 x 10(-5) M) induced concentration-dependent rises in 45Ca2+ uptake in the ovine uterine artery, from a basal level of 30.5 +/- 3.5 muMoles/kg wet tissue to peak levels of 91.1 +/- 9.2 and 84.2 +/- 8.1 muMoles/kg wet tissue, respectively. The Ca2+ influx evoked by 5-HT and DOM was inhibited by ketanserin in a concentration-dependent manner. Methiothepin (2.5 x 10(-7) M) also inhibited 5-HT-induced (2.5 x 10(-6) M) Ca2+ influx by 86%. No antagonism was found with 2.5 x 10(-6) M of 3-tropanyl-3,5-dichlorobenzoate (MDL 72222). The contraction elicited to 5-HT (10(-6) M) and DOM (10(-6) M) was blocked by D600 (10(-6) M) which also blocked the contraction produced to KCl (9 x 10(-2) M). Amrinone (10(-5) M) had no inhibitory effect on these contractions. In accord with the results of the contraction study, D600 (2.5 x 10(-6) M) blocked the Ca2+ influx stimulated by 5-HT (2.5 x 10(-6) M) and amrinone (2.5 x 10(-5) M) failed to inhibit 5-HT-induced Ca2+ influx. Nifedipine (2.5 x 10(-6) M) did not antagonize the influx of Ca2+ induced by 5-HT. Sodium nitroprusside inhibited the 5-HT-induced Ca2+ influx, indicating that at least part of its inhibitory effect on the vasoconstriction evolved by 5-HT is due to the inhibition of the influx of Ca2+.

DOM 2,5-Dimethoxy-4-Methylamphetamine

Effects of ultrasound and trolamine salicylate phonophoresis on delayed-onset muscle soreness.

The purpose of this study was to determine the effects of ultrasound and phonophoresis using an anti-inflammatory-analgesic cream (trolamine salicylate) on delayed-onset muscle soreness (DOMS). Repeated eccentric contractions were used to induce DOMS in the elbow flexors of 40 college-aged women. Subjects were then assigned randomly to one of four groups: (1) group 1 (n = 10) received sham ultrasound using placebo cream, (2) group 2 (n = 10) received sham ultrasound using trolamine salicylate cream, (3) group 3 (n = 10) received ultrasound using placebo cream, and (4) group 4 (n = 10) received ultrasound using trolamine salicylate cream. Subjects were treated on 3 consecutive days. Muscle soreness and active elbow range of motion were assessed daily prior to each treatment. The subjects in group 3 experienced an increase in DOMS, whereas no increase in soreness was observed in the subjects in group 4. The authors concluded that ultrasound enhanced the development of DOMS but that this enhancement was offset by the anti-inflammatory-analgesic action of salicylate phonophoresis. These findings suggest that salicylate phonophoresis may be useful in clinical situations in which it is desirable to administer ultrasound without increasing inflammation.

Adult

A physiological role for sporadic interruptions of the dopaminergic tone in the genesis of big mass prolactin pulses.

The present studies were designed to evaluate pulsatile PRL secretion after the establishment of either a continuous dopaminergic input or a complete blockade of the dopaminergic inhibitory tone. Adult female rats on estrus and male rats implanted with indwelling jugular cannulae were bled at 3-min intervals for a 3-h period. Bromocriptine (CB-154) and domperidone (DOM) were administered sc and iv, respectively. The administration protocol used for both treatments produced either a continuous dopaminergic input (CB-154 treatment) or a complete dopaminergic blockade (DOM treatment). Pulse analysis was performed on the data series using the algorithm Detect. In both estrous female and male rats, dopaminergic receptor activation by CB-154 reduced peak and trough values, pulse amplitude, area under the pulse, and mean PRL levels. In contrast, a complete dopamine (DA) receptor blockade by DOM increased these parameters. Domperidone treatment increased pulse frequency and reduced pulse interval and duration. Bromocriptine, however, differentially affected some pulsatility parameters depending on the sex of the rats. In females, CB-154 did not alter any of the qualitative parameters (frequency, pulse interval, and duration) of pulsatile PRL secretion. In contrast, in male rats the treatment reduced frequency and duration while increasing pulse interval. CB-154 reduced basal PRL levels in male rats, whereas in estrous females this parameter was not altered. PRL pulses were further evaluated by frequency distribution analysis, using the area under the pulses divided by the baseline to normalize the data due to treatment-induced differences in baselines. This calculation allows the estimation of the amount of hormone released per pulse over the baseline. In both estrous female and male rats, two classes of PRL pulses were identified. One class corresponded to pulses containing a small mass of hormone [small mass pulses (SM)], while the others were characterized by pulses containing a large mass of hormone [big mass pulses (BM)]. Interestingly, both the dopaminergic agonist CB-154 and the dopaminergic antagonist DOM dramatically diminished BM pulse incidence in both estrous female and male rats. In fact, BM pulses were practically absent in both experimental groups. To further substantiate this notion, animals of each experimental group were assigned to one of the following categories: animals depicting BM and SM pulses or rats presenting solely SM pulses.(ABSTRACT TRUNCATED AT 400 WORDS)

Activity Cycles

Effects of chronic domperidone treatment on rat conditioned avoidance behavior.

The effects of chronic administration of domperidone (DOM), a peripherally acting anti-emetic and hyperprolactinemic D2-dopaminoceptor antagonist, on active and inhibitory conditioned behavior were tested on male and female rats. DOM (4 mg/kg) was injected ip daily either for 5 or 30 days. Although treatment for 5 days failed to affect experimental parameters, treatment for 30 days impaired the performance of active conditioned avoidance of female, but not male, rats. This effect was no longer observed 7 days after ending treatment. No effects of DOM treatment were observed on active conditioned avoidance of male rats or on inhibitory conditioned behavior of all rats. These data suggest that female rats are more susceptible to the hyperprolactinemic effects of DOM than male rats. However, an influence of estrous cycle interruption cannot be rejected.

Animals

5HT-2 mediation of acute behavioral effects of hallucinogens in rats.

In rats tested during their first exposure to a Behavioral Pattern Monitor chamber, acute injections of the 5HT-2 agonists mescaline, quipazine, 2,5-dimethoxy-4-iodoamphetamine (DOI), 2,5-dimethoxy-4-methylamphetamine (DOM), or 2,5-dimethoxy-4-ethylamphetamine (DOET) produced an inhibition of locomotor and investigatory behavior during the first 30 min of the test session. This suppression of exploratory behavior was attenuated when rats were familiarized with the testing chamber prior to the administration of DOI. Hence, as previously observed with both LSD and DOM, 5HT-2 agonists appear to potentiate the normal neophobic reaction to a novel environment. The mixed 5HT-1 and 5HT-2 agonist 5-methoxy-N,N-dimethyltryptamine (5MeODMT) also produced a decrease in activity when animals were tested in the novel environment. However, as previously found with 5HT-1A agonists, this effect was unchanged when animals were tested in the familiar environment and may therefore reflect a generalized sedation. The receptor specificity of these differential effects of 5HT-1 and 5HT-2 agonists in this paradigm was tested by assessing the ability of selective 5HT-2 antagonists to block the effects of the agonists. A dose of the 5HT-2 antagonist ketanserin which had no effect by itself significantly reduced the behavioral effects of mescaline, DOM, and quipazine. Similarly, the selective 5HT-2 antagonist ritanserin blocked the effect of quipazine. In contrast, ketanserin had no significant effect on the suppression of activity produced by the 5HT-1A agonist 8-hydroxy-2(di-n-propylamino)tetralin (8OHDPAT).(ABSTRACT TRUNCATED AT 250 WORDS)

DOM 2,5-Dimethoxy-4-Methylamphetamine

Characterization of serotonergic receptors mediating contraction of ovine umbilical artery.

Responses to serotonergic agonists were studied in isolated umbilical arteries obtained from fetal lambs within 2 weeks of term. The order of potency of the agonists was determined to be 2,5-dimethoxy-4-methyl-amphetamine (DOM) greater than 5-hydroxytryptamine (5-HT) greater than alpha-methyl-5-HT greater than 1-(3-chlorophenyl) piperazine = m-trifluoromethyl-phenylpiperazine greater than 8-hydroxy-dipropylaminotetralin greater than 2-methyl-5-HT greater than 1-(2-methoxyphenyl) piperazine. Variations in the sensitivity and potency of the agonists results primarily from the variation in the affinity for the 5-HT2 receptor and less so in the efficacy, alpha-Methyl-5-HT was a full agonist compared to 5-HT. The others were partial agonists. The mean KA values for 5-HT and DOM were 4.71 +/- 0.62 x 10(-7) and 0.36 +/- 0.04 x 10(-7) M, respectively. Contractions to 5-HT and DOM were antagonized by ketanserin with pA2 values being 9.4 and 9.1, respectively, suggesting that they act on the same receptor and that their responses are mediated by 5-HT2 receptors. Contractile responses to 8-hydroxy-dipropylaminotetralin, 2-methyl-5-HT and the phenylpiperazines [m-trifluoromethyl-phenylpiperazine and 1-(3-chlorophenyl) piperazine] were also blocked by ketanserin (10(-8) M), indicating that contractions produced by these agonists were mediated by 5-HT2 receptors. No antagonism by MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) of responses to 5-HT indicates that 5-HT3 receptors are not present in this tissue.

DOM 2,5-Dimethoxy-4-Methylamphetamine

Changes in the responsiveness of prolactin secretion to dopaminergic blockade and TRH stimulation throughout sexual maturation in men.

The pituitary prolactin (PRL) response to domperidone (DOM; a dopaminergic antagonist) and TRH administration in human males during different stages of sexual maturation was investigated. Dopaminergic blockade caused an immediate and significant PRL release in all subjects, regardless of the stage of pubertal development. Even though the mean values of peak PRL levels, magnitude of PRL response (delta PRL) and areas under the PRL curve were not significantly different among the different groups, all these parameters showed a clear tendency to increase in parallel to the stage of pubertal development, as indicated by significant positive correlations between age and pubertal stage of the subjects and the magnitude of their PRL response to DOM (r = 0.661, p less than 0.01 and r = 0.536, p = 0.01, respectively). Significant positive correlations also were found between the serum sex steroid hormone concentrations and the PRL response to dopaminergic blockade (r = 0.774, p = 0.02 and r = 0.554, p = 0.01, respectively). In contrast to these findings, no significant differences or tendencies were detected in the PRL responses to TRH among the different subject groups. The different patterns of PRL response to DOM and TRH throughout male puberty might be due to differences in pituitary thresholds for sex steroids between the dopamine- and TRH-dependent intracellular pools.

Adolescent

MR imaging-guided muscle biopsy for correlation of increased signal intensity with ultrastructural change and delayed-onset muscle soreness after exercise.

To determine if there is a correlation between the degree of delayed increase in signal intensity (SI) of muscle after exercise on magnetic resonance (MR) images and the amount of ultrastructural (ULS) injury and delayed-onset muscle soreness (DOMS), MR imaging-guided muscle biopsy was performed to obtain tissue from the legs of nine sedentary subjects 48 hours after downhill running on a treadmill. The degree of soreness was subjectively graded. T1-weighted, spin-density, T2-weighted, and short inversion time inversion-recovery images were obtained before and after biopsy, at 48 and 96 hours after exercise, respectively. The delayed SI increase of muscle on images obtained before biopsy was subjectively graded and measured. The degree of ULS injury was determined with electron micrographs. Serum creatine kinase levels were obtained before and up to 144 hours after exercise at 24-hour intervals. The measured SI, SI grades, and DOMS grades were correlated with the degree of ULS injury. Linear regression analysis revealed poor correlation between the DOMS grades and the degree of ULS injury and good correlation between the SI grade and the degree of ULS injury.

Adult

Effect of downhill running on motoneuron pool excitability.

The purpose of this study was to compare alterations in motoneuron pool excitability after eccentric-biased (ECC-B) downhill running exercise with non-biased (NO-B) level running exercise. Six male subjects (25-34 yr) participated in the study, which included ECC-B exercise (-10% grade) and NO-B exercise (0% grade) at 50% of maximal O2 uptake for 20 min. The control trial consisted of 20 min of quiet rest with all subjects participating in all conditions (repeated measures). Motoneuron pool excitability was measured by the Hoffman reflex (H-wave), which was expressed as a ratio (H/M ratio) of the maximal electrically stimulated muscle action potential (M-wave). NO-B exercise resulted in a 9.3 +/- 2.7% (SE) reduction in the H/M ratio. ECC-B exercise resulted in a 24.6 +/- 5.7% reduction in the ratio (P less than 0.05 for both). The two exercise treatment conditions were also significantly different from one another (P less than 0.05). Twenty-four-hour postexercise H/M ratios were similar to baseline (P greater than 0.05). Postexercise subjective muscle soreness assessment (DOMS) produced significant increases in DOMS of 36 and 166% immediately and 24 h after exercise, respectively, for the ECC-B trial only (P less than 0.001). The data show that ECC-B exercise results in greater postexercise H/M ratio reductions than NO-B exercise and that H/M ratio changes post-ECC-B exercise are not solely associated with DOMS.

Action Potentials

Acute inflammation: the underlying mechanism in delayed onset muscle soreness?

It is well documented in animal and human research that unaccustomed eccentric muscle action of sufficient intensity and/or duration causes disruption of connective and/or contractile tissue. In humans, this appears to be associated with the sensation of delayed onset muscle soreness (DOMS). During the late 1970's, it was proposed that this sensation of soreness might be associated with the acute inflammatory response. However, subsequent research failed to substantiate this theory. The present article suggests that the results of much of the research concerning DOMS reflect events typically seen in acute inflammation. Similarities between the two events include: the cardinal symptoms of pain, swelling, and loss of function; evidence of cellular infiltrates, especially the macrophage; biochemical markers such as increased lysosomal activity and increased circulating levels of some of the acute phase proteins; and histological changes during the initial 72 h. In the final section of this paper, a theoretical sequence of events is proposed, based on research involving acute inflammation and DOMS.

Acute Disease