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Monoamine depletion attenuates the REM sleep deprivation-induced increase in clonidine response in the forced swimming test.

Effect of monoamine depletion on the REM sleep (REMs) deprivation-induced increase in clonidine response in the forced swimming test was investigated. Mice were deprived of REMs by the small pedestal method. Clonidine HCl (10-1000 micrograms/kg, IP), an alpha 2-adrenoceptor agonist, dose dependently increased swimming activities in group-housed and socially isolated mice used as the control groups. The dose-response relationship shifted to the left following REMs deprivation (ED50 values in the group-housed, isolated, and REMs-deprived mice were 250, 200, and 27 micrograms/kg, respectively). Monoamine depletion, induced by reserpine (5 mg/kg, IP) plus alpha-methyl-p-tyrosine (250 mg/kg, IP), did not produce any changes in the effects of clonidine in the control groups. However, in REMs-deprived mice, monoamine depletion significantly decreased the effect of 100 micrograms/kg clonidine, but not that of 300 micrograms/kg clonidine on swimming activity. These results indicate that clonidine-induced increase in swimming activity in the forced swimming test is mainly mediated by postsynaptic alpha 2-adrenoceptor, and that endogenous noradrenaline in the brain plays an important role in the increase of clonidine response following REMs deprivation treatment. The neuronal mechanism of the increase in clonidine response is discussed.

Adrenergic alpha-2 Receptor Antagonists↗

Insulin and glucagon secretion in swimming mice: effects of adrenalectomy and chemical sympathectomy.

Swimming-stress is known to inhibit glucose-stimulated insulin secretion and stimulate glucagon secretion. In the present study, in mice, we investigated the relative contribution of sympathetic nerves and the adrenals to these effects. Mice were pretreated either with adrenalectomy or chemical sympathectomy induced by i.v. injection of 6-hydroxydopamine (6-OHDA), which destroys sympathetic nerve terminals. Two days later, the mice were injected i.v. with either glucose (5.6 mmol/kg) or saline, immediately before being subjected to 2 min swimming-stress or 2 min resting. Directly thereafter, blood was sampled. In normal controls, swimming inhibited glucose-stimulated insulin secretion and elevated plasma glucagon levels (P less than 0.01). Both these responses were absent both in adrenalectomized and in chemically sympathectomized mice. We also found that in resting animals, adrenalectomy reduced plasma levels of glucagon (P less than 0.05) and glucose (P less than 0.01), and that in adrenalectomized mice, swimming lowered basal plasma insulin levels (P less than 0.05). Furthermore, 6-OHDA-treatment elevated basal plasma glucagon levels (P less than 0.01). Thus, we show that, in the mouse, the inhibition of glucose-stimulated insulin secretion and the stimulation of glucagon secretion that occur during swimming-stress are both dependent on mechanisms requiring both the adrenals and intact sympathetic nerve terminals.

Adrenalectomy↗

Neuromodulatory effects of TRH upon swim and cholinergic analgesia.

In addition to short-acting analgesic actions by itself and modulation of analgesic responses induced by endogenous opioids and neurotensin, central administration of thyrotropin-releasing hormone (TRH) potentiates footshock analgesia. The present study evaluated the effects of TRH upon the neurohormonally-mediated though nonopioid analgesia induced by swims in rats. Intracerebroventricular TRH (10 and 50 micrograms) dose-dependently potentiated swim (21, 15, 2 degrees C baths) analgesia on the tail-flick test, an effect which was not due to the hypothermic or basal pain threshold changes. Intravenous (8 mg/kg) TRH potentiated swim (21 degrees C) analgesia; the 600:1 difference in potency between routes strongly suggests central sites of neuromodulatory action. Intracerebroventricular diketopiperazine (50 micrograms), a TRH metabolite, and RX77368 (50 micrograms), a TRH analogue, also potentiated swim (21 degrees C) analgesia, effects also independent of hypothermia and basal reactivity to pain. Finally, given the excitatory interaction between TRH and acetylcholine as well as the cholinergic involvement in swim analgesia, intracerebroventricular TRH potentiated pilocarpine (10 mg/kg, IP) analgesia.

Acetylcholine↗

Metabolic effects of swimming velocity and water temperature in the muskrat (Ondatra zibethicus).

Metabolic rates, VO2, were studied in four muskrats (Ondatra zibethicus) swimming in a water channel at velocities of 0.2 to 0.75 m/s in water at temperatures of 25 and 30 degrees C. At both water temperatures, VO2 increased linearly with increasing swimming velocity. The VO2 was higher for muskrats swimming in water at 25 than 30 degrees C. The metabolic performance of swimming appears to be influenced by the interaction of swimming velocity and water temperature.

Animals↗

Supersensitivity to isoprenaline and epinephrine in right atria isolated from rats submitted to a single swimming session.

1. The effects of swim-induced stress on rat atrial norepinephrine content, plasma corticosterone level and pacemaker sensitivity to catecholamines were studied. 2. Swimming for 50 min reduced the atrial norepinephrine content and induced a long-lasting increase in the plasma corticosterone level. 3. Pacemakers isolated from swim stressed rats showed supersensitivity to the chronotropic effect of isoprenaline. Sensitivity to norepinephrine was not significantly altered. Bilateral adrenalectomy or metyrapone pretreatment prevented the development of swimming-induced supersensitivity to isoprenaline. After in vitro denervation and addition of cocaine supersensitivity to epinephrine was demonstrated. 4. It is concluded that corticosterone, at least partially, mediates the supersensitivity to isoprenaline and epinephrine in pacemaker isolated from acutely swim stressed rats.

Adrenalectomy↗

Effects of the potential antidepressant dihydroergosine in rats forced to swim: influence on plasma corticosterone.

The potential antidepressant properties of the ergot alkaloid dihydroergosine (DHESN) were studied in rats forced to swim in a restricted space. DHESN (50 mg/kg, intraperitoneally) reduced the duration of immobility in rats forced to swim 1 hr after administration. This effect was still present after 48 hr, but 7 hr. In non-swimming rats, the same dose of DHESN increased the plasma corticosterone concentration when administered 1 hr prior to sacrifice, but was without effect 48 hr after administration. In rats forced to swim, DHESN elicited two opposite effects. One hr following a single administration, it increased plasma secretion of corticosterone, whereas administered 48 hr prior to forced swimming, it decreased plasma corticosterone. These results, along with our previous data, give evidence that DHESN might possess antidepressant properties.

Animals↗

Swimming performance and energy metabolism of rainbow trout, common carp and gibel carp respond differently to sublethal copper exposure.

We compared the effects of sublethal waterborne copper exposure on swimming performance and respiration rates in rainbow trout, Oncorhynchus mykiss, with those in less sensitive cyprinid species such as common carp, Cyprinus carpio, and gibel carp, Carassius auratus gibelio. These cyprinids are considerably more resistant to Cu intoxication, and differ from trout in swimming performance and respiratory behaviour. Critical swimming speed (U(crit)), oxygen consumption, plasma ammonia and muscle ammonia, lactate and pH were measured during a 28-day sublethal exposure to 1 microM Cu. U(crit) decreased with 48, 31 and 13% within the first 12-24 h for rainbow trout, common and gibel respectively. Gibel carp recovered quickly and experienced no further reduction in swimming performance. Recovery of swimming capacity in rainbow trout and common carp was only partial. All three species displayed similar plasma ammonia peaks in the first hours to days, and a more gradual muscle ammonia accumulation over time. Whereas no signs of respiratory stress occurred in rainbow trout, common carp experienced a transient reduction in oxygen consumption combined with anaerobic metabolism after 24 h of exposure. At the same time, oxygen consumption was also reduced in gibel carp, but no signs of anaerobic metabolism were detected. Cu accumulated quickly to similar levels (36-39 microg g(-1) dry weight at day 3) in the gills of all three species, after which accumulation leveled off. Liver tissue of rainbow trout had a high Cu level from the start, and Cu concentration did not show any additional accumulation. In contrast, common carp liver showed a significant Cu accumulation from day 3 onwards, while accumulation in gibel livers was much slower and was significant from day 7 onwards. Interestingly, Cu accumulation patterns in plasma and kidney revealed a possibly important role for the kidney in Cu homeostasis of gibel carp.

Ammonia↗

Structure of the rat behaviour in the forced swimming test.

Forced swimming test (FST) or 'behavioural despair' test is a useful screening for antidepressant drugs. The FST predictability has been improved by a number of procedural modifications. Description of the behavioural microstructure in FST may help to delineate innovative protocols. Thus, counts of all behaviours emitted during FST in rats (four-month-old Wistar male, n = 63) were recorded and examined by Markovian sequential analysis (MSA) and principal components analysis (PCA). In a second experiment, rats (n = 28) were tested in an open field test (OFT) followed a week later by FST; behaviours in both tests were recorded and analysed by two correlation methods (Pearson's test and sliding window correlation). The descriptive ethological analysis displayed counts of swimming and immobility increased over the course of the test, whereas climbing behaviour decreased. The MSA revealed the occurrence of immobility was predicted by swimming, climbing, and diving behaviours whereas the immobility predicted the occurrence of swimming behaviour and headshakes. The PCA showed duration of immobility and climbing loaded into one component and duration of immobility and swimming loaded into another one. Low as well high levels of climbing behaviour were positively correlated with motor activity in the OFT. In brief, the present data suggest there are at least two different factors that grouped variables related to the behavioural despair in the FST. In addition, altered motor activity could be predicted by the frequency of climbing behaviour recorded in the FST.

Animals↗

Liver PPARalpha and UCP2 are involved in the regulation of obesity and lipid metabolism by swim training in genetically obese db/db mice.

Swim training for 6 weeks significantly decreased body weight gain, adipose tissue mass, and adipocyte size in both sexes of genetically obese db/db mice compared with their respective sedentary controls. Swim training also caused significant decreases in serum levels of free fatty acids, triglycerides, and total cholesterol in both sexes of obese mice. Concomitantly, hepatic mRNA levels of peroxisome proliferator-activated receptor alpha (PPARalpha) target enzymes responsible for mitochondrial and peroxisomal fatty acid beta-oxidation were significantly increased by swim training. Moreover, mRNA levels of uncoupling protein 2 (UCP2) in liver were also markedly increased by swim training. In conclusion, these results suggest that swim training-induced transcriptional activation of hepatic PPARalpha target enzymes and UCP2 may effectively prevent body weight gain, adiposity, and lipid disorders caused by leptin receptor deficiency in both sexes of mice.

Adipose Tissue↗

Energetics of swimming by the ferret: consequences of forelimb paddling.

The domestic ferret (Mustela putorius furo) swims by alternate strokes of the forelimbs. This pectoral paddling is rare among semi-aquatic mammals. The energetic implications of swimming by pectoral paddling were examined by kinematic analysis and measurement of oxygen consumption. Ferrets maintained a constant stroke frequency, but increased swimming speed by increasing stroke amplitude. The ratio of swimming velocity to foot stroke velocity was low, indicating a low propulsive efficiency. Metabolic rate increased linearly with increasing speed. The cost of transport decreased with increasing swimming speed to a minimum of 3.59+/-0.28 J N(-1) m(-1) at U=0.44 m s(-1). The minimum cost of transport for the ferret was greater than values for semi-aquatic mammals using hind limb paddling, but lower than the minimum cost of transport for the closely related quadrupedally paddling mink. Differences in energetic performance may be due to the amount of muscle recruited for propulsion and the interrelationship hydrodynamic drag and interference between flow over the body surface and flow induced by propulsive appendages.

Animals↗

Cardiac function and critical swimming speed of the winter flounder (Pleuronectes americanus) at two temperatures.

Using Transonic flow probes and a uniquely designed swimming flume, we directly measured cardiac parameters (Q, cardiac output; SV, stroke volume; and fH, heart rate) in winter flounder (Pleuronectes americanus) before and during critical swim speed (Ucrit) tests at 4 and 10 degrees C. Resting Q, SV and fH averaged 9.8 ml min(-1) kg(-1), 0.5 ml kg(-1) (1.0 ml g ventricle(-1)) and 21 beats min(-1) at 4 degrees C and 15.5 ml min(-1) kg(-1), 0.5 ml kg(-1) (0.95 ml g ventricle(-1)) and 34 beats min(-1) at 10 degrees C (Q10 values of 2.13, 0.91 and 2.35, for Q, SV and fH, respectively). Cardiac output, SV and fH increased by approx. 170%, 70% and 60% at both temperatures during the Ucrit test. However, cardiac parameters generally reached near maximal levels almost immediately upon swimming and remained at these levels until Ucrit (0.65 +/- 0.06 bl s(-1) at 4 degrees C and 0.73 +/ -0.07 bl s(-1) at 10 degrees C). This rapid rise in cardiac function to near maximal levels did not appear to be the result of stress alone, as Q only fell slightly when flounder were swum for 75 min at < 0.4 bl s(-1), speeds at which they appeared to swim comfortably. Our results suggest that both Q and Ucrit have been significantly overestimated in flatfishes, and that "lift-off"/slow swimming is energetically expensive. Furthermore, they show that maximum and resting stroke volume (per g of ventricle) are extremely high in the flounder as compared with other teleosts.

Animals↗

Stressors affect the response of male and female rats to clomipramine in a model of behavioral despair (forced swim test).

Aim of the present study was to evaluate the effects of physical stressors (electric foot-shocks) on effect of the antidepressant drug, clomipramine and plasma corticosterone levels in male and female rats tested in a model of behavioral despair (forced swim test,). Male and female rats of the Wistar strain were injected with clomipramine (50 mg/kg, i.p.) or saline. A group of animals also received electric shocks of different intensity and duration of 24, 5 and 1 h before being subjected to forced swim test. At the end of behavioral procedures, vaginal smears were assessed in all female animals and data on immobility time were plotted according to the ovarian cycle phase. After decapitation, corticosterone plasma levels were measured by radioimmunoassay in both male and female rats. Application of mild shocks (5 ms, 0.1 mA) significantly reduced immobility time in forced swim test of untreated male rats and augmented clomipramine effect on this parameter. Moderate shocks of higher intensity or duration (5 ms, 1.0 mA) also resulted in decreased immobility time of untreated male rats, but in reduced effect of clomipramine treatment. Furthermore, application of severe shocks (10 ms, 1.0 mA) increased the immobility time in untreated animals and totally abolished clomipramine effect in forced swim test. Untreated non-shocked female rats in proestrous and estrous phases exhibited a longer immobility time as compared to diestrous animals. Immobility time appeared to be generally higher when mild, moderate or severe shocks were applied prior to behavioral testing in proestrous and estrous animals, while the behavioral response of diestrous and metestrous animals did not differ from that of controls. Clomipramine effect on immobility time was generally reduced by application of shocks of every strengths. Stress-induced plasma corticosterone levels surge correlated with intensity and duration of shocks in both male and female rats, but clomipramine treatment generally blunted the hormonal response. However, severe shocks were followed by a surge of plasma corticosterone levels in both male and female clomipramine-treated rats. These results demonstrate that duration and intensity of stressful stimuli may deeply affect the behavioral response of rats in forced swim test and influence clomipramine effect in this behavioral model depending on gender-based variables, probably of the hormonal type. Plasma corticosterone levels correlate with the behavioral response to clomipramine treatment suggesting that reactivity of hypothalamus-pituitary-adrenal axis to stress may be involved in the antidepressant effect of this drug.

Animals↗

Swimming constraints and arm coordination.

Following Newell's concept of constraint (1986), we sought to identify the constraints (organismic, environmental and task) on front crawl performance, focusing on arm coordination adaptations over increasing race paces. Forty-two swimmers (15 elite men, 15 mid-level men and 12 elite women) performed seven self-paced swim trials (race paces: as if competitively swimming 1500m, 800m, 400m, 200m, 100m, 50m, and maximal velocity, respectively) using the front crawl stroke. The paces were race simulations over 25m to avoid fatigue effects. Swim velocity, stroke rate, stroke length, and various arm stroke phases were calculated from video analysis. Arm coordination was quantified in terms of an index of coordination (IdC) based on the lag time between the propulsive phases of each arm. This measure quantified three possible coordination modes in the front crawl: opposition (continuity between the two arm propulsions), catch-up (a time gap between the two arm propulsions) and superposition (an overlap of the two arm propulsions). With increasing race paces, swim velocity, stroke rate, and stroke length, the three groups showed a similar transition in arm coordination mode at the critical 200m pace, which separated the long- and mid-pace pattern from the sprint pace pattern. The 200m pace was also characterized by a stroke rate close to 40strokemin(-1). The finding that all three groups showed a similar adaptation of arm coordination suggested that race paces, swim velocity, stroke rate and stroke length reflect task constraints that can be manipulated as control parameters, with race paces (R(2)=.28) and stroke rate (R(2)=.36) being the best predictors of IdC changes. On the other hand, only the elite men reached a velocity greater than 1.8ms(-1) and a stroke rate of 50strokemin(-1). They did so using superposition of the propulsion phases of the two arms, which occurred because of the great forward resistance created when these swimmers achieved high velocity, i.e., an environmental constraint. Conversely, the elite women and mid-level men had shorter stroke lengths and maintained a time gap between the propulsions of the two arms throughout the increase in paces, with gender and expertise explaining 9% and 8.3% of the IdC changes, respectively. These results indicate that arm coordination cannot be interpreted solely from the IdC value but should be considered from the perspective of task, environmental, and organismic constraints. These constraints can serve as control parameters in experiments aimed at gaining insight into changes in arm coordination during the front crawl. In this context, catch-up coordination, which is often considered as a mistake, was seen to be an adaptation to a relative constraint.

Analysis of Variance↗

Skin-friction drag analysis from the forced convection modeling in simplified underwater swimming.

This study deals with skin-friction drag analysis in underwater swimming. Although lower than profile drag, skin-friction drag remains significant and is the second and only other contribution to total drag in the case of underwater swimming. The question arises whether varying the thermal gradient between the underwater swimmer and the pool water may modify the surface shear stress distribution and the resulting skin-friction drag acting on a swimmer's body. As far as the authors are aware, such a question has not previously been addressed. Therefore, the purpose of this study was to quantify the effect of this thermal gradient by using the integral formalism applied to the forced convection theory. From a simplified model in a range of pool temperatures (20-30 degrees C) it was demonstrated that, whatever the swimming speeds, a 5.3% reduction in the skin-friction drag would occur with increasing average boundary-layer temperature provided that the flow remained laminar. However, as the majority of the flow is actually turbulent, a turbulent flow analysis leads to the major conclusion that friction drag is a function of underwater speed, leading to a possible 1.5% reduction for fast swimming speeds above 1m/s. Furthermore, simple correlations between the surface shear stress and resulting skin-friction drag are derived in terms of the boundary-layer temperature, which may be readily used in underwater swimming situations.

Computer Simulation↗

Long-term effects of nicotine on the forced swimming test in mice: an experimental model for the study of depression caused by smoke.

Large evidence showing an association between depression and tobacco smoking is known. Nicotine is the active chemical responsible for smoking addiction, and its withdrawal may induce in smokers greater sensitivity to stress. Our aim has been to investigate the links between tobacco addiction and depression by studying the long-term effects of repeated administration of nicotine followed by dependence, to forced swimming test, serotonin content and 5-HT(1A) expression in diencephalon. Dependence has been induced by daily subcutaneous injection in mice of nicotine (2mg/kg four injections daily) for 15 days and assessed after nicotine withdrawal with an abstinence scale; control animals received daily subcutaneous injection of saline for the same period. Experiments on forced swimming test have been carried out at t=0 (last day of nicotine or saline treatment), and 15, 30, 45 and 60 days after saline or nicotine withdrawal. Both control mice and nicotine mice have been pre-treated with oral 5-hydroxy-tryptophan (12.5-50mg/kg), precursor of serotonin, before forced swimming test. Nicotine mice have shown on forced swimming test a significant increase of immobility time compared to control mice. This increase was not evident in nicotine mice treated with 5-hydroxy-tryptophan and treatment with the selective serotonin receptorial antagonist WAY 100635 (WAY) abolished 5-hydroxy-tryptophan effects. Evaluation of diencephalic serotonin, performed at t=0 showed an increase of diencephalic serotonin content, while serotonin measured 15, 30, 45 and 60 days after nicotine withdrawal, was significantly reduced in nicotine mice compared to control mice. Western blot analysis showed a great reduction of 5-HT(1A) receptor expression in nicotine mice measured at t=0 (last day of treatment) and at 15 and 30 days after nicotine withdrawal compared to control mice. Our results show that (i) behavioural alterations estimated with forced swimming test and (ii) changes in diencephalic serotonin content and 5-HT(1A) receptor expression, are present since nicotine is withdrawn even after a long time, suggesting a role of serotonin in mood disorders eventually occurring following smoking cessation.

Animals↗

Differential effects of forced swim-stress on the corticotropin-releasing hormone and vasopressin gene transcription in the parvocellular division of the paraventricular nucleus of rat hypothalamus.

Corticotropin-releasing hormone (CRH) and vasopressin (AVP) colocalize in the parvocellular division of the paraventricular nucleus of the hypothalamus (PVN). We examined the effect of forced swim-stress on the CRH and AVP primary transcript (hnRNA) levels in the rat PVN by semi-quantitative in situ hybridization. CRH hnRNA increased markedly following 10-min swim-stress and returned to the basal level by 2 h. AVP hnRNA in the parvocellular division of the PVN, where AVP colocalizes with CRH, did not change significantly immediately after the swim-stress, but it did increase significantly 2 h after the stress. Pretreatment with dexamethasone abolished the increases in CRH and AVP hnRNA levels after the swim-stress. The present results demonstrate the differential effects of forced swim-stress on the CRH and AVP gene transcription in the parvocellular PVN, confirming the diverse response of the dual peptide-containing system in the face of acute stressful events.

Animals↗

A role for GABAA receptors in the modulation of Paramecium swimming behavior.

The presence in Paramecium of gamma-aminobutyric acid A-type receptors (GABA(A)) and the capability of the protozoon to synthesize and release the GABA neurotransmitter into the environment have already been demonstrated. This study investigates the involvement of the GABA(A) complex in the swimming control of the ciliated protozoon. The GABA(A) receptors were pharmacologically activated by the selective agonist muscimol and the effect on Paramecium primaurelia swimming behavior was analyzed. Paramecium normally swims forward, but the activation of GABA(A) receptors induced a peculiar response, characterized by alternate periods of whirling and forward swim. This effect was inhibited by the GABA(A) selective antagonists bicuculline and picrotoxin in a dose-dependent manner. Moreover, the application of benzodiazepines did not enhance the agonist action but only reduced it. Response to muscimol was also suppressed by nimodipine, a selective antagonist of dihydropyridine-sensitive calcium channels. This inhibition suggests that an inflow of calcium ions through L-type channels mediates the muscimol-induced swimming behavior.

Animals↗

Central suppressive effect of octreotide on the hyperglycemic response to 2-deoxy-D-glucose injection or cold-swim stress in awake rats: possible mediation role of hypothalamic noradrenergic drive.

Somatostatin (SRIH) and its analog have been reported to act within the central nervous system to suppress the hyperglycemic response to a variety of neural stimuli. On the other hand, the hyperglycemic response to 2-deoxy-D-glucose (2-DG) injection or cold-swim stress is well demonstrated to be closely associated with an increase in hypothalamic noradrenergic neuronal activity (NNA). To evaluate whether the suppression of the hypothalamic NNA response could be involved in the central mechanism whereby a SRIH analog inhibits the hyperglycemic response, octreotide, a clinically used long-acting octapeptide SRIH analog, was administered into the third cerebral ventricle of awake rats prior to the intraperitoneal injection of 2-DG or cold-swim stress. Hypothalamic noradrenaline (NA) and its neuronal metabolite, 3,4-dihydroxyphenylethyleneglycol (DHPG), were analyzed, and the ratio of DHPG to NA was used as an index of NNA. Intracerebroventricular (i.c.v.) pretreatment with octreotide suppressed the 2-DG-induced increase in hypothalamic NNA, accompanied by the inhibition of the serum glucose, NA and adrenaline responses. This suppressive effect of octreotide was dose-dependent. Similarly, i.c.v. pretreatment with octreotide prevented the hypothalamic NNA response to cold-swim stress, accompanied by a blockade of the increases in serum glucose, NA and adrenaline. A close relationship between hypothalamic NNA and serum glucose emerged from these studies. Intraperitoneal pretreatment with octreotide had no significant effect on the hyperglycemic or hypothalamic NNA response to 2-DG injection. These findings suggest that the inhibitory effect of octreotide on the hypothalamic NNA response to 2-DG injection or cold-swim stress is associated with the simultaneous suppression of the hyperglycemic response. Supporting the concept that hypothalamic NNA contributes to the modulation of blood glucose in stressful conditions, it is suggested that the suppression of the hypothalamic NNA response is, at least in part, involved in the central mechanism by which octreotide inhibits the hyperglycemic response to 2-DG injection or cold-swim stress.

Animals↗