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PubMed2002

Effects of different frequencies of transcranial magnetic stimulation (TMS) on the forced swim test model of depression in rats.

BACKGROUND: Repetitive transcranial magnetic stimulation has been demonstrated in humans as well as in animal models to have an antidepressant effect, but the optimal frequency of stimulation is not known. We examined this question in a rat model of depression. METHODS: Young male Sprague-Dawley rats were allocated to two placebo (restraint and sham transcranial magnetic stimulation), one active control (imipramine), and four transcranial magnetic stimulation groups at 1, 5, 15 and 25 Hz and 1000 stimuli each. The Porsolt Swim Test was performed on day 1 (experiment 1). In an extension (experiment 2), the treatments were repeated on days 2 through 5, and the Swim Test repeated on days 3, 5, and 7. RESULTS: After one treatment session, all transcranial magnetic stimulation groups had significantly reduced immobility times compared with sham stimulation (p =.000), but the higher frequencies (15 and 25 Hz) did not differ significantly from lower (1 and 5 Hz) frequencies. After three sessions, all transcranial magnetic stimulation groups were different from placebo, and the rapid transcranial magnetic stimulation groups had lower immobility times than the slow transcranial magnetic stimulation groups (p =.035). After five sessions, only 15- and 25-Hz groups were different from control, and on day 7, only the 25-Hz group had reduced immobility. There was an overall difference between fast and slow transcranial magnetic stimulation (p =.010), and 1 Hz was different from the other three transcranial magnetic stimulation conditions (p =.016). CONCLUSIONS: Repetitive transcranial magnetic stimulation reduces immobility time in the Forced Swim Test model of depression, suggesting an antidepressant effect, which is evident at a range (1-25 Hz) of frequencies. With repeated administration, the findings suggest that the antidepressant effect of the higher frequencies, as for imipramine, is likely to be sustained, although the model used for this (i.e., repeating the Swim Test) requires further validation.

Animals↗
PubMed1997

Effects of antidepressants on phencyclidine-induced enhancement of immobility in a forced swimming test in mice.

We have previously found that repeated phencyclidine (PCP) treatment enhances the immobility induced by forced swimming and suggested that this behavioral change could be used as a model of the negative symptoms, particularly depression, of schizophrenia. The present study attempted to examine the effects of antidepressants on the depressive states (immobility) induced by forced swimming in mice repeatedly treated with PCP, compared with those in mice repeatedly treated with saline. In mice repeatedly treated with saline, desipramine (5 and 10 mg/kg) and imipramine (5 and 10 mg/kg) significantly attenuated immobility, whereas mianserin (5-20 mg/kg) and clomipramine (10 and 50 mg/kg) had no affect. In mice repeatedly treated with PCP, the enhancing effect of PCP on immobility was attenuated by mianserin (5-20 mg/kg) at doses which did not have any effect in saline-treated mice, and by desipramine at higher doses (20 and 50 mg/kg). However, imipramine (5-20 mg/kg) and clomipramine (10-50 mg/kg) did not affect PCP-induced enhancement of immobility. In the biochemical study, the content of 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HIAA/5-hydroxytryptamine (5-HT) ratio in the prefrontal cortex in mice repeatedly treated with PCP, but not with saline, following the forced swimming test were significantly increased, compared with those in the corresponding control mice (which did not perform the test). The present findings suggest that the depressive states induced by the forced swimming in mice repeatedly treated with PCP are less sensitive to acute treatment with tricyclic antidepressants, and this may be due to increase in 5-HT turnover. Antidepressants such as mianserin, which have the 5-HT2 receptor antagonist properties, may be useful for the treatment of negative symptoms of schizophrenia.

Animals↗
PubMed2000

Pulmonary oedema induced by strenuous swimming: a field study.

The purpose of the study was to document the incidence and recurrence rate of pulmonary oedema induced by strenuous swimming (SIPO), and to study the changes in relevant physiological parameters. Thirty-five young men were repeatedly examined over a 2-month period after a swimming time trial in the open sea. A tentative diagnosis of SIPO was made when the swimmer reported shortness of breath accompanied by cough. Twenty-nine events of SIPO were diagnosed in 21 individuals (60% incidence). Oxygen saturation was significantly reduced in SIPO. Mean forced vital capacity (FVC) and FEV(1) were significantly lower in the severe SIPO group. Also, mean FVC and mid-expiratory flows (FEF(25-75%)) obtained 12 months earlier during screening for the programme were lower in individuals who later had SIPO. The ratios of post-swim FVC and FEV(1) values to the corresponding selection examination values were lower in the severe SIPO group. Thus volumes decreased in the SIPO group, besides being lower at the start. Shortness of breath and coughing following strenuous swimming were related to hypoxaemia and reduction in lung volumes, suggesting pulmonary oedema. SIPO was a common and often recurrent phenomenon. Lower initial lung volumes and flows might predict future susceptibility to SIPO.

Adolescent↗
PubMed1998

An action spectrum for the light-dependent inhibition of swimming behavior in newly hatched white sturgeon, Acipenser transmontanus.

Newly hatched white sturgeon (Acipenser transmontanus) yolk-sac larvae are negatively phototactic, photokinetic and geotactic--seeking cover in the substrate during daylight hours. If cover is unavailable and the light intensity is low, they move into the water column and alternate periods of rapid, upward swimming with periods of quiescence during which they sink. In the dark they swim almost continuously. A flash of light inhibits swimming activity totally for a period dependent on the light intensity. Using this observation, we obtained an action spectrum for swimming inhibition for 30 newly hatched larvae. This action spectrum is best fit by a single visual pigment with absorbance maximum at 537 nm. The lack of red sensitivity fits well with previous work showing that red-sensitive photoreceptor cells are absent in young sturgeon. The possible significance of red insensitivity is discussed from both ecological and practical standpoints.

Animals↗
PubMed2000

Anticonvulsive effect of swim stress in mice.

To explore the possible involvement of glucocorticoids in the previously observed anticonvulsive effect of swim stress, mice were, prior to administration of convulsants, subjected to treatments that diminish or enhance plasma corticosterone levels. Aminoglutethimide, the inhibitor of steroid synthesis, failed to modify convulsant doses of picrotoxin, but enhanced threshold doses of pentylenetetrazole producing myoclonus and death, both in unstressed and stressed animals. The same drug prevented the effect of stress on pentylenetetrazole-induced running bouncing clonus (RB clonus) and abolished the appearance of tonic hindlimb extension (THE). Doses of kainic acid producing convulsions and death were not affected by stress, but they were enhanced by aminoglutethimide. Corticosterone administration could not imitate the effect of swim stress. Finasteride, a 5 alpha-reductase inhibitor, did not interfere with the effect of stress on picrotoxin-induced convulsions. Swim stress failed to modify the binding of the convulsant t[3H]-butylbicycloorthobenzoate [3H]TBOB, to washed mouse forebrain membranes. The results confirmed an anticonvulsant effect of swim stress against convulsions produced by GABA-related convulsants, but they do not support the hypothesis suggesting the involvement of glucocorticoids or neurosteroids in this effect.

5-alpha Reductase Inhibitors↗
PubMed2003

Diet influences cocaine withdrawal behaviors in the forced swimming test.

The effects of drugs of abuse might depend on several environmental factors, among them the individual's feeding habits. It was our objective to study the influence of the diet on cocaine acute behavioral effects and during the first 5 days of withdrawal after prolonged treatment. Rats were fed a balanced diet, high-protein diet, high-carbohydrate diet or high-fat diet from weaning to adulthood. Adult rats were injected with 15 mg/kg cocaine 24, 5 and 1 h before the forced swimming retest or the drug was administered daily during 15 days and the animals were evaluated in the forced swimming test on five daily occasions after drug withdrawal. Diets alone did not induce significant behavioral differences in locomotion, immobility, swimming, climbing or head shakes. Acute cocaine reduced immobility during the forced swimming test and increased locomotion demonstrating a nonspecific antiimmobility effect related to hyperactivity. Acute cocaine reduced head shakes of rats fed high-protein and high-carbohydrate diets. After cocaine withdrawal, head shakes were decreased for rats fed any of the diets and rats were more immobile if fed a high-fat diet and were less immobile if fed a high-protein or high-carbohydrate diet. In conclusion, differences in the amounts of macronutrients in the diet may cause different behavioral outcomes after acute cocaine and during cocaine withdrawal.

Animals↗
PubMed1998

Comparison of behavioral effects of moclobemide and deprenyl during forced swimming.

The present study compared the antiimmobility effects of l-deprenyl (DEP) and moclobemide (MOC) to the classic antidepressant imipramine (IMI), using an ethological approach. To investigate the degree of MAO-B inhibition by DEP and MOC, combination of treatments of ineffective doses of phenylethylamine (PHEA) with DEP or with MOC were administered in three doses before immobility was tested in the forced-swimming paradigm. Tests were videotape recorded for analysis of the frequency and duration of the behaviors during the procedure. There was a significant, dose-dependent decrease in immobility duration and an increase in mobility duration of rats treated with IMI. Both active behaviors of climbing and swimming were equally enhanced by the tricyclic antidepressant, climbing behavior composing 75% of the mobile behaviors. The intermediate doses of the MAOIs tested, DEP 0.25 mg/kg and MOC 30 mg/kg, decreased immobility and increased mobility. The antiimmobility effect of DEP was due to longer climbing behavior while MOC enhanced swimming duration. No behavioral changes were seen with the administration of the lower and higher doses of the MAOI. Potentiation of the antiimmobility effects was observed when ineffective doses of PHEA and of DEP or MOC were administered in combination. Differences between the MAO inhibitors on the active behaviors were also observed when administered with PHEA; DEP and PHEA significantly increased climbing and MOC and PHEA increased swimming. This preclinical evaluation of selective MAO inhibitors indicates that both MAO-A and MAO-B inhibitors have antidepressant effects. However, to clearly demonstrate that these antiimmobility effects are a consequence of increased brain concentrations of any one of the several monoamines implicated in the mechanism of action of DEP or MOC should be the subject of future studies.

Animals↗
PubMed2003

Open space swimming test to index antidepressant activity.

Depression is characterized by a lack of "motivation" rather than a lack of "physical space" to move around. This study was designed to evaluate predictivity of an open space swimming test for antidepressant activity of various antidepressants in rats. Without drug treatment, rats showed a significant reduction in the distance moved (increased immobility) over successive trials in an open space water pool. Three major classes of antidepressants and a selective serotonin reuptake inhibitor (SSRI) were tested. Repeated treatment (10 mg/kg x 3 per day) of imipramine, a prototypical tricyclic antidepressant, iproniazid, a monoamine oxidase inhibitor, mianserin, an atypical antidepressant, and alaproclate, an SSRI, all significantly reduced the immobility. These results suggest that the open space swimming test is highly predictive of antidepressant action and is more sensitive to the drug treatments. The measurement is more objective than that of the forced swimming test and does not involve judging and scoring the animals' movement or lack of movement by investigators. The demonstrated effectiveness of three major types of antidepressants and an SSRI suggests that the effects on the test are not restricted to a particular underlying molecular mechanism of action. Thus, this swimming test shows promising potential as a screen for novel antidepressants and, perhaps, for revealing some of the underlying pathophysiology of depression.

Alanine↗
PubMed2001

Impairment of mysid (Neomysis integer) swimming ability: an environmentally realistic assessment of the impact of cadmium exposure.

Neomysis integer (Crustacea: Mysidacea), a euryhaline member of the hyperbenthos of the upper reaches of European estuaries, has been identified as a suitable animal for assessing the impacts of chemical pollutants on these estuarine regions. In this study, the effect of a 7 day pre-exposure to environmentally relevant concentrations of cadmium (0.5 and 1.0 microg l(-1)) on the swimming behaviour of N. integer was examined using an annular flume. Cadmium speciation at two salinities (1 and 10 per thousand) that dominate these upper estuarine regions was modelled to ensure mysids were exposed to the same concentration of the toxic free-ion at each salinity. There was no significant difference in the swimming behaviour of mysids exposed to the same free-ion cadmium concentration at the two different salinities. At each salinity, exposure to 0.5 microg Cd2+ (aq) l(-1)resulted in fewer mysids moving forward into the current (normal behaviour) at free stream velocities typical of their natural habitat (e.g. 3-9 cm s(-1)) than non cadmium-exposed mysids. At these low current speeds, cadmium-exposed mysids were either able to maintain position or were swept by the current. The same general responses were recorded for mysids exposed to 1.0 microg Cd2+ (aq) l(-1)except that more mysids showed disrupted swimming ability compared with 0.5 microg Cd2+ (aq) l(-1). At higher current speeds (>12 cm s(-1)), current velocity was the dominant factor affecting mysid swimming behaviour and there was no effect of cadmium on mysids maintaining position. Exposure to cadmium also caused significant disruption of the hyperbenthic behaviour of N. integer and more cadmium-exposed individuals were in the water column than control mysids; this result was more variable at 10 per thousand than 1 per thousand. Results indicate that exposure to cadmium concentrations of 0.5 microg Cd2+(aq) l(-1)would result in displacement of N. integer from its optimum region within the estuarine environment. This conclusion would not be achieved from standard LC(50) tests (e.g. 7 day LC50 = 2.95 microg Cd2+ (aq) l(-1)), highlighting the value of behavioural disruption as a sensitive indicator of environmental chemical contamination.

Animals↗
PubMedDate not supplied

Progesterone reduces immobility in rats forced to swim.

BACKGROUND: Among its behavioral actions, progesterone reduces anxiety in several species including humans; however, any antidepressant-like properties remain to be explored. METHODS: In the present study, Wistar rats received injections (i.p.) of progesterone (0.20-3.0 mg/kg) 24 and 2 h before being submitted to the forced swim, a test in which antidepressants regularly reduce immobility and exert few or no actions on locomotor activity. In order to discard the cumulative effects of progesterone and a possible effect from the repetition of the swimming test, all animals received one of several progesterone doses in a different sequence following a completely randomized experimental intrasubject design. RESULTS: Ovariectomy did not modify immobility in the forced swim test as compared to control tests practiced before surgery. A dose of 0.80 mg/kg strongly reduced the total time of immobility in forced swim test (p < 0.001), but did not modify locomotor activity. In a drug-free control test applied 1 week after the last injection of progesterone, immobility returned to the higher values observed in the control tests. CONCLUSIONS: From these results, it is concluded that progesterone may possess some anti-depressant-like activity.

Animals↗
PubMed1998

On inappropriately used neuronal circuits as a possible basis of the "loop-swimming" behaviour of fish under reduced gravity: a theoretical study.

One hypothesis for the explanation of the so-called "loop-swimming" behaviour in fish when being subjected to reduced gravity assumes that the activities of the differently weighted otoliths of the two labyrinths are well compensated on ground but that a functional asymmetry is induced in weightlessness, resulting in a tonus asymmetry of the body and by this generating the "loop-swimming" behaviour. The basis of this abnormal behaviour has to be searched for in the central nervous system (cns), where the signal-transduction from the inner ear- related signal internalisation to the signal response takes place. Circuits within the CNS of fish, that could possibly generate the "loop-swimming", might be as follows: An asymmetric activation of vestibulospinal circuits would directly result in a tonus asymmetry of the body. An asymmetric activation of the oculomotor nucleus would generate an asymmetrical rotation of the eyes. This would cause in its turn asymmetric images on the two retinas, which were forwarded to the diencephalic accessory optic system (AOS). It is the task of the AOS to stabilize retinal images, thereby involving the cerebellum, which is the main integration center for sensory and motor modalities. With this, the cerebellar output would generate a tonus asymmetry of the body in order to make the body of the fish follow its eyes. Such movements (especially when assuming an open loop control) would end up in the aforementioned "loop-swimming" behaviour.

Animals↗
PubMed1999

Injuries in competitive swimming.

Competitive swimming is commonly thought to be an injury-free sport. Traumatic and overuse injuries do occur, especially if one includes accidents occurring to both athletes and spectators, and accidents resulting from some of the newer diving and starting techniques. United States Swimming, Incorporated, the national governing body for competitive swimming, and provider of insurance coverage for most of the swimming clubs in the United States, keeps track of reported injuries to club members, and requires specific safety accreditation for member coaches. These data provide an informative view on injuries to competitive swimmers.

Athletic Injuries↗
PubMed2003

Female rats show an increased sensibility to the forced swim test depressive-like stimulus in the hippocampus and frontal cortex 5-HT1A receptors.

Affective disorders are more common in women. The forced swim test acts like a depressive stimulus. Hippocampus and frontal cortex 5-HT1A receptors of female and male Wistar rats subjected to the forced swim test were compared with a sham group. The forced swim test diminishes (P<0.05) the hippocampus 3H-8OH-DPAT bound in the female rats (184+/-16 fmol/mg protein) with respect to the male rats (309+/-41 fmol/mg protein) and to the female sham rats (255+/-20 fmol/mg protein). The forced swim test increases the frontal cortex 5-HT1A receptors in the female rats with respect to the female sham group (40.4+/-5 versus 24.7+/-4 fmol/mg protein, P<0.05). An increased sensibility of the 5-HT1A receptors to depressive-stimulus may be one mechanism underlying the higher prevalence of depression in female.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Swim-stress but not opioid withdrawal increases expression of c-fos immunoreactivity in rat periaqueductal gray neurons which project to the rostral ventromedial medulla.

Expression of c-fos-like immunoreactivity has been used as a marker for neuronal activation and is elevated in the periaqueductal gray following stressful and noxious stimuli, and opioid withdrawal. The present study examined the staining of c-fos-like immunoreactivity following opiate withdrawal or swim-stress (2.5-3 min at 21 degrees C) in periaqueductal gray neurons of the rat which had projections to and through the rostral ventromedial medulla identified by microinjection of the retrograde tracer, Fast Blue, into the nucleus raphe magnus prior to development of morphine dependence. Both naloxone-precipitated withdrawal and swim-stress increased numbers of neurons expressing c-fos-like immunoreactivity in periaqueductal gray. Naloxone-precipitated withdrawal did not increase the number of double-labelled neurons in periaqueductal gray suggesting that neurons excited during opioid withdrawal do not project to the ventromedial medulla. In contrast, swim-stress produced increases in double-labelled neurons in periaqueductal gray suggesting that many periaqueductal gray neurons activated by swim-stress project to the ventromedial medulla. These findings suggest that naloxone-precipitated withdrawal does not activate ventrolateral periaqueductal gray neurons which are involved in descending inhibitory pathways, consistent with behavioural observations that naloxone-precipitated withdrawal is qualitatively opposite to electrical and chemical stimulation of the ventrolateral periaqueductal gray. The results are also consistent with a role of descending projections from periaqueductal gray in stress-induced antinociception.

Animals↗
PubMed2003

Effects of acute and chronic administration of selective monoamine re-uptake inhibitors in the rat forced swim test.

The rat forced swim test (FST) is a model that is used extensively as a screening test for antidepressant activity. It has previously been reported that thorough analysis of behaviour in this model reveals two distinct types of active response - climbing and swimming - and that these are separately evoked by re-uptake inhibitors selective for noradrenaline (NA) and serotonin (5-HT), respectively. In the present study, utilising re-uptake inhibitors selective for NA, talsupram, and 5-HT, 5-chloro-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)- phthalan (Lu 10-134-C), we examined if this scoring technique could detect the antidepressant potential of a selective serotonin re-uptake inhibitor (SSRI), and whether re-uptake inhibitors selective for distinct monoamine systems induce exclusive behavioural responses. We also analysed if chronic antidepressant administration for three weeks was more effective than acute treatment. We found Lu 10-134-C (40 mg/kg; PO) to be behaviourally active in this paradigm. Although treatment with talsupram (40 mg/kg; PO) resulted solely in climbing behaviour, Lu 10-134-C induced both climbing and swimming behaviour. However, chronic pre-treatment with either re-uptake inhibitor (20 mg/kg; twice daily; PO) failed to augment the response observed with acute treatment. Similarly, chronic administration of either compound was without effect on the basal, or stress-induced, serum corticosterone concentrations or anterior pituitary (AP) preproopiomelanocorticotropin (POMC) mRNA expression. These results suggest that selective monoamine re-uptake inhibition produces distinct, but not necessarily exclusive, behavioural responses in the forced swim test.

Adrenergic Uptake Inhibitors↗
PubMed2001

Antidepressant-like properties of zinc in rodent forced swim test.

The effects of zinc, the N-methyl-D-aspartate glutamate receptor inhibitor, were studied in mice and rats using the forced swim test. Zinc (ZnSO4) in a dose of 30 mg/kg and imipramine (30 mg/kg), reduced the immobility time in the forced swim test in both species. Moreover, combined treatment in this test with zinc and imipramine at their ineffective doses (1 and 5 mg/kg, respectively) induced a statistically significant effect in rats. The doses active in the forced swim test reduced (in mice) or did not affect (in rats) locomotor activity. The results obtained indicate that zinc induces an antidepressant-like effect and enhances the effect of imipramine in the forced swim test, suggesting a potential antidepressant activity of zinc in humans.

Animals↗
PubMed2000

Effect of diazepam on the immune response of rats exposed to acute and chronic swim stress.

To examine the effect of the anti-stress agent diazepam on the immune response, rats were exposed either to acute swim stress, i.e., swimming once only for 30 minutes (non-trained swimmers), or to chronic stress with gradual progressive training for 6 weeks (trained swimmers). Both groups of animals were divided into subgroups treated before swimming with and without diazepam, 1 mg/kg, administered i.m. The phagocytic capacity and superoxide anion generation of the peritoneal macrophages was examined. In addition, the proliferative response of the splenic cells (splenocytes) to concanavalin A (Con A) and phytohemagglutinin (PHA), as well as the serum corticosterone levels were investigated. Diazepam abolished increased superoxide anion production in both non-trained and trained swimmers. In non-trained swimmers, the number of latex particles internalized by each cell was decreased and further reduced by the drug. In trained rats treated with diazepam, the percentage of phagocytosing cells remained reduced compared to controls, whereas the drug prevented a decrease in the engulfing capacity of individual cells. Diazepam lowered the suppressed proliferative response of the splenocytes to PHA found in non-trained swimmers. It is concluded that diazepam modifies the immune response of rats exposed to acute and chronic swim stress.

Animals↗
PubMed2002

Nonpeptidic delta-opioid receptor agonists reduce immobility in the forced swim assay in rats.

The present study examined the effect of opioid receptor agonists in the rat forced swim assay. The delta-opioid receptor agonists SNC80 ((+)-4-[(alpha R)-alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide) and (+)BW373U86 ((+)-[1(S*),2 alpha,5 beta]-4-[[2,5-dimethyl-4-(2-propenyl)-1-piperazinyl] (3-hydroxyphenyl)methyl]-N,N-diethyl-benzamide dihydrochloride) produced a decrease in immobility indicating an antidepressant-like effect. At antinociceptive doses, neither the kappa-opioid selective agonist CI977 (5R-(5 alpha,7 alpha,8 beta)-N-methyl-N-[7-(1-pyrrolidinyl-1-oxaspiro[4,5]dec-8-yl]-4-benzofuranacetamide) showed a change in immobility that was identifiable by dose, nor were changes in immobility seen with morphine. A delta-opioid mechanism of action in the forced swim assay was likely since naltrindole prevented the effects of both delta-agonists. When compared to desipramine and fluoxetine, SNC80 was more active with a single dose whereas both desipramine and fluoxetine produced greater effects with subchronic dosing (3 doses). All three compounds were active when administered before the initial swim exposure. SNC80 was, however, more effective following a single dose than by subchronic administration demonstrating both a fast onset of activity and potential tolerance. Thus, delta-agonists differ from typical antidepressants in the forced swim assay.

Animals↗