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PubMed2006

The impact of moderate daily alcohol consumption on aggression and the formation of dominance hierarchies in rats.

RATIONALE AND OBJECTIVE: Group-housed male rats form social hierarchies, and under these conditions, it has been reported that subordinate (SUB) rats consume more alcohol than dominant (DOM) rats. We tested the hypothesis that a history of drinking alcohol would cause SUB rats to consume even greater amounts of alcohol. METHODS: Male Long-Evans rats were trained to drink 10% alcohol or a sucrose/quinine solution equal in calories for 1 h/day using a sucrose-fading procedure. Subsequently, rats were housed in colonies (four males, two females) in a visible burrow system (VBS) for 14 days. Individual control male rats were housed in a tub cage with one female. Rats were removed from the VBS (or control environment) daily and given 1 h to drink alcohol or sucrose/quinine. RESULTS: Colonies given daily access to sucrose/quinine formed clear DOM/SUB relationships in all measured parameters. Alcohol-drinking colonies failed to establish a dominance hierarchy and displayed little aggression, with an average of 14.6 +/- 6.1 offensive attacks compared with 58.5 +/- 12.3 attacks carried out by DOM sucrose/quinine rats. During VBS housing, alcohol and sucrose/quinine intake decreased independent of housing environment or social status. CONCLUSIONS: Contrary to prior reports of the effect of alcohol on aggressive behavior, moderate daily alcohol intake before and during VBS housing reduced aggression and precluded the formation of a dominance hierarchy in rats.

Aggression↗

PubMed2003

Complexation as the most important factor in the fate and transport of heavy metals in the Dnieper water bodies.

The results of long-term investigations of the concentrations of dissolved forms of some heavy metals (Mn, Cu, Zn, Pb, Cr, Cd) and their species in the water of the Dnieper reservoirs and the Dnieper-Bug estuary are considered. Chemiluminescent methods, anodic stripping voltammetry, membrane filtration, ion-exchange, and gel-permeation chromatography were used for study of the speciation of the metals. It has been found that binding of heavy metals into complexes with dissolved organic matter (DOM) is the dominant factor of their stabilization in solution. The molecular weight distribution of organic metal complexes and their chemical nature, as well as the potential complexing ability of DOM were investigated. Humic substances, particularly fulvic acids, play a major role in the complexation. These ligands bind from 45 to 80% of metals in the form of organic complexes. Metal complex compounds of relatively low molecular weight (<5 kDa) predominated in the organic complexes.

Journal Article↗

PubMed2005

Effects of dissolved and complexed copper on heterotrophic bacterial production in San Diego bay.

Bacterial abundance and production, free (uncomplexed) copper ion concentration, total dissolved copper concentration, dissolved organic carbon (DOC), total suspended solids (TSS), and chlorophyll a were measured over the course of 1 year in a series of 27 sample "Boxes" established within San Diego Bay. Water was collected through a trace metal-clean system so that each Box's sample was a composite of all the surface water in that Box. Bacterial production, chlorophyll a, TSS, DOC, and dissolved copper all generally increased from Box 1 at the mouth of the Bay to Box 27 in the South or back Bay. Free copper ion concentration generally decreased from Box 1 to Box 27 presumably due to increasing complexation capacity within natural waters. Based on correlations between TSS, chlorophyll a, bacterial production or DOC and the ratio of dissolved to free Cu ion, both DOC and particulate (bacteria and algae) fractions were potentially responsible for copper complexation, each at different times of the year. CuCl2 was added to bacterial production assays from 0 to 10 microg L(-1) to assess acute copper toxicity to the natural microbial assemblage. Interestingly, copper toxicity appeared to increase with decreases in free copper from the mouth of the Bay to the back Bay. This contrasts the free-ion activity model in which higher complexation capacity should afford greater copper protection. When cell-specific growth rates were calculated, faster growing bacteria (i.e. toward the back Bay) appeared to be more susceptible to free copper toxicity. The protecting effect of natural dissolved organic material (DOM) concentrated by tangential flow ultrafiltration (>1 kDa), illite and kaolinite minerals, and glutathione (a metal chelator excreted by algae under copper stress) was assessed in bacterial production assays. Only DOM concentrate offered any significant protection to bacterial production under increased copper concentrations. Although the potential copper protecting agents were allowed to interact with added copper before natural bacteria were added to production assays, there may be a temporal dose-response relationship that accounts for higher toxicity in short production assays. Regardless, it appears that effective natural complexation of copper in the back portions of San Diego Bay limits exposure of native bacterial assemblages to free copper ion, resulting in higher bacterial production.

Bacteria↗

PubMed1999

Differential Dissolved Organic Nitrogen Availability and Bacterial Aminopeptidase Activity in Limnic and Marine Waters.

Abstract Nitrogen often limits primary production in marine ecosystems and its loading from terrestrial sources is the major cause of enhanced coastal eutrophication worldwide. About 70% of nitrogen transported by rivers globally is dissolved organic nitrogen (DON). Therefore, terrestrial DON is potentially an important component of the N dynamics in aquatic ecosystems, but the bioavailability of this organic nitrogen is poorly known. Bacterial extracellular hydrolysis of polymers is a bottleneck in the utilization of natural dissolved organic matter, mostly consisting of high molecular weight compounds. To study the bacterial utilization and extracellular enzymatic hydrolysis of DON, we developed a bioassay employing natural DON as the only N source, and N as the limiting nutrient. Bacterial cell density and activity of an unspecific aminopeptidase (AMPase) were followed in the cultures. Natural DON stimulated the cell-specific AMPase activity. Furthermore, refractory and humus-rich DOM caused a stronger stimulation than labile DOM. We propose that the previously reported inhibitory effect of humic substances on enzyme activity was outweighed by the induction of enzyme synthesis caused by refractory substrates. AMPase activity and the estimated DON bioavailability were more than twofold higher in seawater than in freshwater with identical substrate additions. This indicates that hydrolysis and turnover of land-derived DON is enhanced when it enters coastal marine waters, enabling it to support elevated bacterioplankton and phytoplankton growth.http://link.springer-ny.com/link/service/journals/00248/bibs/38n3p264.html</hea

Journal Article↗

PubMed2002

Desmin and actin alterations in human muscles affected by delayed onset muscle soreness: a high resolution immunocytochemical study.

Lack of staining for desmin in muscles in animal models of eccentric exercise has been suggested to reflect disruption of the desmin intermediate filament network and proposed to cause disruption of the myofibrillar apparatus and deterioration of muscle fibers. In a recent study, we examined muscle biopsies from persons who had performed different eccentric exercise protocols, which induced delayed onset muscle soreness (DOMS). We were unable to verify that loss of staining for desmin was a feature of sore muscles. Nevertheless, we observed changes in the desmin cytoskeleton, but the meaning of the observations was not conclusive. In the present study, a high resolution immunocytochemical method was used to investigate the changes of desmin and actin in human muscles following a bout of eccentric exercise that lead to DOMS 2-3 days post-exercise. Biopsies were taken before exercise and 1 h and 2-3 and 7-8 days after exercise. Phalloidin, a ligand that labels filamentous actin, and anti-desmin antibodies were used to stain semithin (approximately 0.5 micro m) cryosections. At 1 h post-exercise, the staining of actin and desmin did not differ from the controls, whereas in biopsies taken 2-3 and 7-8 days after exercise, 12.5% (SD 5.8%) and 6.1% (SD 2.3%) fibers showed areas of increased staining for actin. Corresponding values for fibers with increased staining for both actin and desmin were 8.7% (SD 3.9%) and 11.4% (SD 4.6%), respectively. We suggest that the increased staining of actin and desmin reflects an increased synthesis of these proteins as part of an adaptation process following the unaccustomed eccentric exercise.

Actins↗

PubMed2005

Comparison between leg and arm eccentric exercises of the same relative intensity on indices of muscle damage.

Many exercise models have demonstrated associations between eccentric muscle actions and muscle damage. However, the magnitude of muscle damage varies among the models. It appears that responses to eccentric exercise are different between leg and arm muscles but this has not been systematically clarified. This study compared leg and arm eccentric exercises of the same relative intensity for indices of muscle damage. Eleven healthy untrained males [Age: 21.2 (1.0) years, Height: 179.4 (3.0) cm, Weight: 78.4 (3.1) kg] performed a sub-maximal eccentric exercise of the knee extensors (LEGS) and the elbow flexors (ARMS), separately. Both LEGS and ARMS consisted of six sets of 12 repetitions with an intensity corresponding to 75% of the predetermined maximal eccentric peak torque (EPT) of each muscle. Range of motion (ROM), delayed onset muscle soreness (DOMS), serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, myoglobin (Mb) concentration, and muscle strength [EPT and isometric peak torque (IPT)] were assessed before and 24, 48, 72, and 96 h following exercise. Significant (P < 0.05) changes in DOMS and ROM were observed up to 96 h after both exercise bouts, and the magnitude of the change was similar between LEGS and ARMS. Increases in CK and Mb were significantly (P < 0.05) larger after ARMS than LEGS at 72 and 96 h post-exercise. EPT and IPT were significantly (P < 0.05) lower than the baseline up to 96 h post-exercise for ARMS but were fully recovered by 96 h post-exercise for LEGS. Decreases in muscle strength were significantly (p < 0.05) larger following ARMS than LEGS at 48, 72, and 96 h post-exercise for EPT, and from 24 h to 96 h post-exercise for IPT. These results suggest that the magnitude of muscle damage is greater and the recovery of muscle function was slower after eccentric exercise of arm elbow flexors than the knee extensors.

Adult↗

PubMed2005

NMDA receptor involvement in the effects of low dose domoic acid in neonatal rats.

We have previously reported that neonatal rats display enhanced sensitivity to domoic acid relative to adults, and that perinatal injections of low doses of domoic acid alter early associational learning in the newborn rat. The current study was designed to further investigate the effects of low dose domoic acid on neonatal odour conditioning and to determine if the observed effects are due in part to an action on NMDA receptors. Groups of rat pups were conditioned to a novel odour on postnatal day (PND) 8, injected with 20 microg/kg domoic acid either alone, or in combination with the NMDA antagonist CPP (or appropriate controls), daily from day 8-14, re-exposed to the conditioning odour or a novel odour on day 9, and tested for odour preference on day 13 using a standard 3-choice paradigm. Results indicated that rats treated with domoic acid spent significantly more time over the conditioning odour than did saline-treated rats when tested on PND 13. This effect was antagonized by concomitant injection of CPP, indicating an involvement of NMDA receptors in the actions of DOM in this paradigm. Rats injected with either saline or CPP alone showed the opposite effect, i.e. a preference for the alternate odour. The results indicate that a very low dose of DOM produces a conditioned odour preference in neonatal rats and that this effect is due in part to NMDA receptor involvement, thereby emphasizing a role for both kainate and NMDA glutamate receptors in implicit memory.

Animals↗

PubMed1991

Domoic acid enhances the K(+)-evoked release of endogenous glutamate from guinea pig hippocampal mossy fiber synaptosomes.

The presynaptic effects of domoic acid (Dom) on hippocampal mossy fiber synaptic transmission were examined using a subcellular fraction enriched in mossy fiber synaptosomes. Domoic acid significantly increased the K(+)-evoked release of endogenous glutamate from superfused guinea pig mossy fiber synaptosomes. The presynaptic facilitation produced by Dom was dose-dependent and was antagonized by the prior application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). At a concentration of 30 microM, both domoic acid and kainic acid significantly increased the extent to which membrane depolarization augmented the availability of cytosolic free calcium in mossy fiber synaptosomes. These results are consistent with the suggestion that domoic acid enhances the release of mossy fiber neurotransmitters in the guinea pig hippocampus through the activation of a CNQX-sensitive presynaptic receptor.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1984

5-HT1 and 5-HT2 binding properties of derivatives of the hallucinogen 1-(2,5-dimethoxyphenyl)-2-aminopropane (2,5-DMA).

The affinities of a series of 1-(2,5-dimethoxyphenyl)-2-aminopropane (2,5-DMA) derivatives, most of which are hallucinogenic in man, and several related agents were determined for rat cortical serotonin (5-HT) binding sites. Competition assays were performed in which these agents were competed for the 5-HT2 binding of [3H]ketanserin, or the 5-HT1 binding of [3H]LSD (in the presence of ketanserin). The R(-)-isomers of DOI, DOM and DON (i.e. the 4-iodo, -methyl and -nitro derivatives of 2,5-DMA) were found to be more potent than their racemates and demonstrated selectivity for 5-HT2 sites. These same agents in competing for [3H]ketanserin binding resulted in Hill coefficients significantly less than unity; computer-assisted analysis indicated a two-state model better fit the data. In the presence of 10(-4) M Gpp(NH)p the competition curve for R(-)-DOI produced a Hill coefficient close to unity. These results are consistent with the hypothesis that certain derivatives of 2,5-DMA, in particular R(-)-DOI, may be potent and selective agonists at 5-HT2 binding sites, sites that may constitute a serotonin receptor that is regulated by a guanine nucleotide regulatory protein. Conversely, the interactions of these agents at 5-HT1 sites was with a lower affinity and a lack of stereoselectivity. Although DOI and DOM are amongst the most potent of these agents as hallucinogens, it is still too premature to draw any conclusions regarding a possible relationship between 5-HT binding and hallucinogenic potency.

Amphetamines↗

PubMedDate not supplied

Profile of drug effects on temporally spaced responding in rats.

A differential reinforcement of low rate schedule was used with rats to test 15 psychotropic drugs. The computer analysis was based on interresponse time (IRT). Mean IRT, IRT standard deviation, median IRT, IRT midrange, modal IRT, frequency of modal IRT, and an efficiency index, in addition to numbers of responses and reinforcements and the IRT histogram were obtained for each rat in each drug test. An increase in number of responses and a peak shift to shorter IRTs in the histograms were observed with amphetamine, methamphetamine, priradrol and nicotine, as reported by many other investigators. Decrease in IRT midrange and less change in number of responses were observed with diazepam and chlordiazepoxide. Long pauses were found with LSD-25, 2,5-dimethoxy-4-methylamphetamine (DOM) and mescaline. In a factor analysis, the following main factors were obtained. High values in factor loading a1 were observed with chlorpromazine, chlordiazepoxide, pentobarbital, imipramine, nialamide, LSD-25, DOM and mescaline. With these drugs, mean IRT and IRT standard deviation were also high. Values for a2, were high with amphetamine, methamphetamine, pipradrol and nicotine. High a3 values were observed in some rats with chlorpromazine, diazepam, chlordiazepoxide, pentobarbital, pipradrol and caffeine. The changes in a3 values were correlated with changes in the IRT midrange. These results may be valuable in classifying new compounds in drug screening programs as being of the amphetamine type, nicotine type, diazepam type of LSD-25 type.

Animals↗

PubMed1981

Central 5-hydroxytryptamine and the effects of hallucinogens and phenobarbital on operant responding in rats.

The present study was designed to examine the role of 5-hydroxytryptamine (5-HT) neurons in the behavioral effects of d-lysergic acid diethylamide (LSD), an indolealkylamine hallucinogen, 2.5-dimethoxy-4-methylamphetamine (DOM) and mescaline, phenethylamine hallucinogens, and phenobarbital, a non-hallucinogen. Male rats, maintained at 70-80% of their free-feeding weights, were trained to press a lever for food pellet reinforcement on a fixed ratio-40 operant schedule. When trained, these rats responded at a constant, rapid rate (approximately 100 responses/min) during daily 40 min test sessions. Administration of hallucinogens caused an abrupt cessation of responding (a "pause"), for some portion of the session. The duration of this pause was dose-dependent for LSD (12.5-100 micrograms/kg), DOM (0.125-1.0 mg/kg) and mescaline (7.1-14.2 mg/kg). On the other hand, phenobarbital (12.5-50 mg/kg) did not cause pausing, but resulted in slowed, erratic intrasession response rates. When the same tests were repeated in rats that had previously received an intracerebroventricular injection of 5,7-dihydroxyptamine (5,7-DHT) the dose-response curves for the pausing induced by all three hallucinogens were shifted to the left, while the behavioral disruption produced by phenobarbital was unaltered. In these animals the 5-HT but not the norepinephrine concentrations was markedly reduced in all brain regions examined. These results suggest that 5-HT neurons are involved with the behavioral effects of hallucinogens but not of phenobarbital.

5,7-Dihydroxytryptamine↗

PubMed1986

Relationship of CNS tryptaminergic processes and the action of LSD-like hallucinogens.

Tryptamine produces pharmacologic effects in man and the chronic spinal dog which are similar to those produced by LSD, mescaline, psilocin, DMT, DOM and DOB. These effects include tachycardia, tachypnea, mydriasis, hyperreflexia, behavioral changes and in man, hallucinations. Chronic spinal dogs treated chronically with LSD became tolerant to its ability to produce mydriasis, tachycardia, tachypnea and hyperreflexia, and were cross tolerant to the ability of tryptamine, psilocin, mescaline, DMT, DOM and DOB to produce these same effects. Further, it was found that the brain and spinal cord contained tryptamine and could release it. Further tryptamine levels were higher in the brainstem and spinal cord above the level of transection in the chronic spinal dog that in intact dogs, and the same in the spinal cord below the level of transection. These observations suggested that there were both ascending and descending tryptaminergic pathways. Supporting this hypothesis were the observations that L-tryptophan also produced hyperreflexia in the acute, but not the chronic, spinal dog and cat, and that L-tryptophan hyperreflexia was antagonized by alpha-methyldopa but not pCPA. These observations and others argue that the spinal cord and brain have tryptaminergic mechanisms which are distinct from serotoninergic mechanisms, and that LSD-like hallucinogens act in part through a tryptaminergic mechanism.

5-Hydroxytryptophan↗

PubMed1988

Interactions between serotonergic agonists and antagonists in rats trained with LSD as a discriminative stimulus.

Drugs purported to have selective affinities for 5-HT1A, 5-HT1B, and 5-HT2 receptors were tested in rats trained with 0.1 mg LSD versus saline. Included were 5-methoxy-dimethyltryptamine (MDMT), 2,5-dimethoxy-4-methyl-amphetamine (DOM), 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), m-trifluoromethylphenyl-piperazine (TFMPP), and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU-24969). Tests were then repeated in the presence of either pizotyline or pirenperone. DOM substituted for LSD and both were blocked by pizotyline and pirenperone. MDMT, 8-OH-DPAT, TFMPP, and RU-24969 substituted less completely and were variably affected by the antagonists. An unexpected result was potentiation of the stimulus or disruptive effects of certain doses of 8-OH-DPAT and TFMPP by pizotyline and pirenperone. The present findings suggest more complex interactions between these drugs than has previously been assumed.

Animals↗

PubMed1988

A preliminary behavioral investigation of PMMA, the 4-methoxy analog of methamphetamine.

The controlled-substance analog N-monomethyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA) may be viewed as being either the 4-methoxy analog of methamphetamine or the N-methyl analog of 1-(4-methoxyphenyl)-2-aminopropane (PMA). Because of its abuse potential, PMMA was examined with regard to (a) its stimulus properties in rats trained to discriminate either 1.0 mg/kg of (+)amphetamine or (+/-)DOM from saline, (b) its toxicity (isolated and aggregated) in mice relative to (+/-)PMA, and (c) its locomotor stimulant activity in mice relative to (+/-)amphetamine, (+/-)methamphetamine, and (+/-)PMA. Racemic PMMA produced neither DOM-like nor, unlike PMA, amphetamine-like stimulus effects. There was no significant difference between the 24-hr isolated (LD50 = 63 mg/kg) and aggregated (LD50 = 53 mg/kg) toxicity, and PMMA did not produce significant locomotor stimulation at doses of up to 30 mg/kg. The present results suggest that while PMMA may produce central effects it does not appear to behave as a simple amphetamine-like agent.

Amphetamine↗

PubMed1992

Further studies on N-methyl-1(3,4-methylenedioxyphenyl)-2-aminopropane as a discriminative stimulus: antagonism by 5-hydroxytryptamine3 antagonists.

Using a standard two-lever operant paradigm, male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg N-methyl-1(3,4-methylenedioxyphenyl)-2- aminopropane (MDMA) from saline using a variable-interval 15-s schedule of reinforcement for food reward. Tests of stimulus antagonism were conducted to further define the mechanism of action of MDMA as a discriminative stimulus. Low doses of the 5-hydroxytryptamine1A (5-HT1A) antagonist NAN-190, the 5-HT2 antagonist pirenperone, and the dopamine antagonist haloperidol were able to somewhat attenuate the MDMA stimulus; however, none of these agents decreased MDMA-appropriate responding to less than 46%. The 5-HT3 antagonists zacopride and LY 278584 (ID50 = 0.02 micrograms/kg) antagonized the MDMA discriminative stimulus. Zacopride also attenuated the stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in DOM-trained animals but not those of (+)amphetamine in (+)amphetamine-trained animals. Several possible mechanistic interpretations are provided but it is concluded that MDMA produces its stimulus effects via a complex mechanism involving both dopaminergic and serotonergic components.

3,4-Methylenedioxyamphetamine↗

PubMed1989

Melatonin modulates the sensitivity of 5-hydroxytryptamine-2 receptor-mediated sleep-wakefulness regulation in the rat.

The interaction between melatonin and two 5-hydroxytryptamine (5-HT2) compounds was studied on sleep patterns in rats. Administration of the 5-HT2 receptor antagonist ritanserin (0.63 mg/kg, i.p.) resulted in a significant increase of deep slow wave sleep (SWS2) and a decrease of paradoxical sleep (PS). The 5-HT2 receptor agonist DOM (1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane) (0.63 mg/kg, i.p.) produced a significant reduction of both SWS2 and PS. Melatonin (1 mg/kg, i.p.) alone did not alter sleep but counteracted the sleep effects induced by ritanserin as well as DOM. It is proposed that melatonin modulates the sensitivity of 5-HT2 receptor-mediated sleep response probably by an indirect route.

Animals↗

PubMed1991

Interaction of 5-bromowillardiine with non-NMDA receptors expressed in Xenopus laevis oocytes injected with chick brain mRNA.

Excitatory amino acid (EAA) receptors were studied in Xenopus laevis oocytes microinjected with 1-day-old chick brain mRNA using a two-electrode voltage clamp technique. EAA agonists could be differentially characterised according to their current/voltage (I/V) relationships; I/V plots to kainate (KA) and domoate (Dom) inwardly rectified at positive membrane potentials whereas quisqualate (QA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and L-glutamate (L-Glu) produced linear I/V plots. Interestingly, the non-NMDA (N-methyl-D-aspartate) agonist, 5-bromowillardiine (BrW), displayed properties similar to KA and Dom. It is proposed that BrW acts as a KA-like agonist on chick EAA receptors expressed in Xenopus oocytes.

Alanine↗

PubMed2005

Static magnetic fields neither prevent nor diminish symptoms and signs of delayed onset muscle soreness.

OBJECTIVE: To determine whether application of a commercially available static magnetic field would alter the signs and/or symptoms of delayed onset muscle soreness (DOMS) produced by exhaustive eccentric exercise. DESIGN: A double-blinded, randomized, and placebo-controlled study, with subjects serving as their own controls. SETTING: An outpatient physical therapy and performance center. PARTICIPANTS: Twenty-three healthy volunteers (18 women; mean age, 30 y; range, 18-40 y; 5 men; mean age, 29 y; range, 19-39 y). INTERVENTION: After exhaustive eccentric exercise of both the right and left elbow flexor muscle groups, subjects received daily treatment with either a 350G magnet or a placebo device for 5 consecutive days. MAIN OUTCOME MEASURES: Outcome variables, including anthropometric measurements, perceived discomfort, and muscle force production, were compared using linear mixed models. RESULTS: Arm circumference, relaxed elbow flexion angle, and pain increased, whereas active elbow flexion angle and maximal isometric torque decreased transiently before returning to near baseline. No significant difference in outcome variables existed between the treated and control arms. Participants reported less pain in both treated and control arms after each session, suggesting a placebo effect. CONCLUSIONS: Static magnetic fields were no more effective than placebo in preventing DOMS.

Adult↗