Forced Swim Task Research Articles

Differences in affective behaviors and hippocampal allopregnanolone levels in adult rats of lines selectively bred for infantile vocalizations

Allopregnanolone, 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP), a progesterone metabolite, is an endogenous neurosteroid mediating affective behaviors via its positive modulation of GABA A receptors. In order to better understand the role of this neurosteroid in individual differences in affective behavior, we used an animal model based on selective breeding for an infantile affective trait, ultrasonic vocalizations (USV). Adult male and female (in either proestrus or diestrus) rats that had been bred for low (low line) or high (high line) rates of USV after maternal separation were tested in a series of affective behavioral tests: open field, emergence, social interaction, defensive freezing, and the Porsolt forced swim task. Concentrations of allopregnanolone in combined hippocampus and amygdala tissue were then measured. low line subjects showed significantly lower anxiety and depression responses in the emergence, open field, and Porsolt forced swim tasks than did high line subjects. Proestrus females exhibited less affective behaviors than diestrus females or males. Allopregnanolone levels in hippocampus/amygdala were significantly higher in low line subjects compared to high line subjects, and in proestrus females compared to diestrus females and males. These data indicate that: (1) affective behaviors in lines selectively bred for an infantile anxiety trait exhibit selection persistence into adulthood; and (2) levels of allopregnanolone in the limbic system parallel selected disparities in affective behavior, suggesting a selection for alterations in the neurosteroid/GABA A receptor system in these lines.

Synergistic interaction between ketoconazole and several antidepressant drugs with allopregnanolone treatments in ovariectomized Wistar rats forced to swim

This article was aimed to investigate the interest of the combination allopregnanolone plus ketoconazole in depression with the time-sampling method in the forced swimming task. Dose–response curves for fluoxetine (0.5, 1.0 or 2.0 mg/kg, twice day, during 2 weeks; i.p.), desipramine (0.5, 1.0 or 2.14 mg/kg, twice a day, during 2 weeks; i.p.), ketoconazole (6.25, 12.5, 25.0 and 37.5 mg/kg, once a day, during 2 weeks; i.p.) and allopregnanolone (0.5, 1.5, 2.0 mg/kg; once a day, during 2 weeks; s.c.) were established. Fluoxetine (1.0 mg/kg, p<0.05; 2.0 mg/kg, p<0.05) or ketoconazole (25.0 mg/kg, p<0.05; 37.5 mg/kg, p<0.05) produced antidepressant-like behavioral changes in swimming, highlighting a serotonergic mechanism while desipramine (1.0 mg/kg, p<0.05; 2.14 mg/kg, p<0.05) or allopregnanolone (1.5 mg/kg, p<0.05; 2.0 mg/kg, p<0.05) increased climbing behavior highlighting noradrenergic or dopaminergic effects. Subthreshold doses of fluoxetine ( p<0.05), desipramine ( p<0.05) or ketoconazole ( p<0.05) synergized with subthreshold doses of allopregnanolone and reduced immobility by increasing climbing. In conclusion, fluoxetine, desipramine, ketoconazole and allopregnanolone produced differential antidepressant-like actions in ovariectomized rats forced to swim. Ketoconazole, fluoxetine or desipramine synergized with allopregnanolone.

Anxiolytic-like actions of leaves of Casimiroa edulis (Rutaceae) in male Wistar rats

Anxiolytic-like actions of an aqueous extract of the leaves of Casimiroa edulis (Ce) La Llave ex Lex. (Rutaceae) were studied in male Wistar rats in the elevated plus-maze test, whether effect on locomotion were studied in the open-field task, and its possible antidepressant-like actions in the forced swimming task. In the elevated plus-maze test, diazepam (Dz) (1.30 mg/kg; P<0.05) and Casimiroa edulis (25.0 mg/kg, P<0.05; 35.0 mg/kg, P<0.05) increased open arms exploration (i.e., anxiolytic-like action). Doses of 45.0 mg/kg ( P<0.05) and 55.0 mg/kg ( P<0.05) of Casimiroa edulis reduced locomotion in the elevated plus-maze test and in the open-field test. In the forced swimming task, desipramine (dmi) (32.0 mg/kg; P<0.05) reduced immobility (i.e., antidepressant-like action). Conversely, as compared to control rats, neither diazepam (Dz) (1.30 mg/kg) nor Casimiroa edulis (25.0 mg/kg) modified immobility in the forced swimming task. However, diazepam ( P<0.05) or Casimiroa edulis ( P<0.05), when co-administered, canceled the antiimmobility actions of desipramine. In conclusion, the leaves of Casimiroa edulis (Rutaceae) produced anxiolytic-like actions in male Wistar rats, with several side actions, namely, reduced locomotion and neutralization of the antidepressant-like actions of desipramine.

Caffeine as a Performance-Enhancing Drug in Rats: Sex, Dose, Housing, and Task Considerations

Past animal studies of the performance-enhancing properties of stimulant drugs, such as caffeine, may have suffered from a number of procedural and ethical problems. For example. the housing condition of the animals was often not taken into consideration. As well, endurance tests, such as the forced swim task, sometimes involved ethically (and procedurally) questionable interference with natural swimming behaviour. Some of the manipulations, such as attaching a weight to the swimming animal's tail to increase the difficulty of the task and using mortality as a dependent variable, seem grotesque, even unnecessary. In this experiment, the performance-enhancing effects of caffeine in a modified forced swim task and a dominance task were evaluated using male and female rats as subjects (N=60), housed in either enriched or isolated environments. Analysis indicated that rats respond to caffeine as an interactive function of sex, housing, dose, and task characteristics. It was concluded that performance-enhancing properties of stimulant drugs may be the result of a complex interplay of variables, making simple generalizations questionable.

Protective effects of pseudoginsenoside-F 11 on methamphetamine-induced neurotoxicity in mice

In the present study, pseudoginsenoside-F 11 (PF 11), a saponin that existed in American ginseng, was studied on its protective effect on methamphetamine (MA)-induced behavioral and neurochemical toxicities in mice. MA was intraperitoneally administered at the dose of 10 mg/kg four times at 2-h intervals, and PF 11 was orally administered at the doses of 4 and 8 mg/kg two times at 4-h intervals, 60 min prior to MA administration. The results showed that PF 11 did not significantly influence, but greatly ameliorated, the anxiety-like behavior induced by MA in the light–dark box task. In the forced swimming task, PF 11 significantly shortened the prolonged immobility time induced by MA. In the appetitively motivated T-maze task, PF 11 greatly shortened MA-induced prolonged latency and decreased the error counts. Similar results were also observed in the Morris water maze task. PF 11 significantly shortened the escape latency prolonged by MA. There were significant decreases in the contents of dopamine (DA), 3,4-dihydroxyphenacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoacetic acid (5-HIAA) in the brain of MA-treated mice. PF 11 could partially, but significantly, antagonize MA-induced decreases of DA. The above results demonstrate that PF 11 is effective in protection of MA-induced neurotoxicity and also suggest that natural products, such as ginseng, might be potential candidates for the prevention and treatment of the neurological disorders induced by MA abuse.

Gestational stress induces post-partum depression-like behaviour and alters maternal care in rats

Gestational stress (GS) produces profound behavioural impairments in the offspring and may permanently programme hypothalamic–pituitary–adrenal (HPA) axis function. We investigated whether or not GS produced changes in the maternal behaviour of rat dams, and measured depression-like behaviour in the dam, which might contribute to effects in the progeny. We used the Porsolt test, which measures immobility in a forced-swim task, and models depression in rodents, while monitoring maternal care (arched-back nursing, licking/grooming, nesting/grouping pups). Pregnant rats underwent daily restraint stress (1 h/day, days 10–20 of gestation), or were left undisturbed (control). On post-parturition days 3 and 4, dams were placed into a swim tank, and time spent immobile was measured. GS significantly elevated immobility scores by approximately 25% above control values on the second test day. Maternal behaviours, in particular arched-back nursing and nesting/grouping pups, were reduced in GS dams over post-natal days 1–10. Adult offspring showed increased immobility in the Porsolt test, and also hypersecreted ACTH and CORT in response to an acute stress challenge. These data show that GS can alter maternal behaviour in mothers, and this might contribute to alterations in the offspring. GS may be an important factor in maternal post-natal depression, which may in turn detrimentally effect the offspring because depressed mothers do not sufficiently care for their offspring.

CAFFEINE AS A PERFORMANCE-ENHANCING DRUG IN RATS: SEX, DOSE, HOUSING, AND TASK CONSIDERATIONS

Past animal studies of the performance-enhancing properties of stimulant drugs, such as caffeine, may have suffered from a number of procedural and ethical problems. For example, the housing condition of the animals was often not taken into consideration. As well, endurance tests, such as the forced swim task, sometimes involved ethically (and procedurally) questionable interference with natural swimming behaviour. Some of the manipulations, such as attaching a weight to the swimming animal's tail to increase the difficulty of the task and using mortality as a dependent variable, seem grotesque, even unnecessary. In this experiment, the performance-enhancing effects of caffeine in a modified forced swim task and a dominance task were evaluated using male and female rats as subjects (N = 60), housed in either enriched or isolated environments. Analysis indicated that rats respond to caffeine as an interactive function of sex, housing, dose, and task characteristics. It was concluded that performance-enhancing properties of stimulant drugs may be the result of a complex interplay of variables, making simple generalizations questionable.

Antidepressant-like actions of pregnancy, and progesterone in Wistar rats forced to swim.

In rats, some behavioral changes occurring during pregnancy related to the presence of progesterone may be analyzed in the forced swimming task (FST), which is designed to test the antidepressant profile of drugs. The present study was aimed to analyze in pregnant rats, in rats after delivery, or in rats after receiving progesterone those behavioral changes displayed in the FST. We hypothesize that pregnancy and progesterone will produce antidepressant-like effects in rats forced to swim. Therefore, pregnant rats (14th, 17th, and 20th days), or rats after delivery (3rd, and 7th days) were tested in the FST. Ovariectomized rats receiving saline (0.9%; i.p.), clomipramine (1.25 mg/kg; i.p.), or desipramine (2.14 mg/kg; i.p.) for 28 days were also tested in the FST. In a second series of experiments, ovariectomized rats receiving vehicle or progesterone (0.5 mg/kg; or 2.0 mg/kg; sc.) were tested in the FST. Locomotion was evaluated in the open field test. Results showed that in the FST: 1) pregnancy (P < 0.05), or progesterone (P < 0.05), or desipramine (P < 0.05), reduced immobility by increasing climbing; 2) clomipramine (P < 0.05) reduced immobility by increasing swimming; 3) rats tested after delivery displayed similar behavior than control rats. A lower locomotion was observed only at the end of pregnancy. In conclusion, results suggest that during pregnancy, a reproductive process characterized by its high levels of progesterone, antidepressant-like effects can be found.

Acute and longer term effects of meso-2,3 dimercaptosuccinic acid (DMSA) on the behavior of lead-exposed and control mice

We investigated the effect of chelating agent meso-2,3 dimercaptosuccinic acid (DMSA_ on spatial learning and forced-swim immobility in Binghamton Heterogeneous Stock (HET) mice. Forced-swim immobility (characterized by increasingly frequent bouts of complete motionlessness in a forced-swim test, i.e., behavioral despair) is reduced by exposure to lead. In Experiment 1, male and female HETs ( n = 81) were assigned to lead-exposed (0.5% lead acetate ad lib in drinking fluid), pair-fed (PF), or water control groups. Six weeks after the termination of lead exposure, half of each group was injected intraperitoneally (IP) with 50 mg/kg DMSA or vehicle once per day for 5 days. Following treatment, all animals were tested for acquisition and extinction in the Morris Water maze, followed by immobility testing in an inescapable forced-swim task. Neither Pb nor DMSA affected Morris maze performance. However, consistent with previously published work, Pb reduced immobility in the forced-water swim relative to both PF and water controls. Additionally, lead-exposed males, but not females, showed sustained improvement following DMSA treatment on immobility measures. Experiment 2 was designed to demonstrate the effect of the above DMSA protocol on blood-Pb, and also examined the immediate effects of DMSA on immobility during treatment. Thus, in Experiment 2, animals were exposed to an identical Pb and DMSA treatment protocol, but the effects of DMSA on immobility during the course of DMSA treatment were measured, and animals were sacrificed immediately after treatment so that blood-Pb measures could be taken. Under these circumstances, DMSA markedly reversed the lead-induced reduction in immobility immediately during the treatment phase. Although DMSA clearly reduced blood-lead in males, its influence on female blood levels was far less. Taken together, the data from these experiments suggest that DMSA ameliorates lead-induced immobility changes in mice, but that gender may modulate DMSA's effect on blood-lead and longer-term behavioral effects. However, further work is needed to clarify the role of gender in response to DMSA.

Stressor-provoked behavioral changes in six strains of mice.

Behavioral changes induced by inescapable shock were examined in six strains of mice. Exposure to shock provoked time-dependent disturbances of shuttle escape performance. In some strains the shock treatment did not affect escape performance, whereas in others profound performance deficits were evident. The inescapable shock treatment likewise induced strain-dependent alterations of performance in a forced-swim task. In most instances the shock treatment initially provoked invigorated responding, but in other strains the shock had no effect or depressed active responding. Finally, Y-maze spontaneous alteration performance was not affected by the shock treatment, although a strain-dependent increase of perseverative responses was evident. The occurrence of a stressor-induced deficit in one task in a particular strain of mouse was not predictive of behavioral alterations in a second task. These data are discussed with respect to animal models of depression and genetic differences associated with the response to stressors.

Acquired immobility response in weaver mutant mice

Weaver mutant mice, contrary to normal littermate controls, did not acquire the immobility response in a forced swimming task. In regard to swimming performance, the weaver mutants swam with less ability but with more vigor than normal mice. Results are discussed in terms of the role of the cerebellum in swimming behavior.

Amphetamine withdrawal: A behavioral evaluation

The effects of withdrawal from long-term amphetamine treatment on intracranial self-stimulation, forced swim-induced immobility, shuttle escape performance, acoustic startle and locomotor activity were evaluated. Mice implanted with stimulating electrodes in the lateral hypothalamus demonstrated stable and reliable rates of self-stimulation responding. After exposure to a chronic schedule of amphetamine treatment response rates were severely depressed. In addition to modifying intracranial self-stimulation responding, amphetamine withdrawal increased the duration of immobility in a forced-swim situation. Although chronic amphetamine exposure induced pronounced behavioral changes in the intracranial self-stimulation and forced swim tasks, drug withdrawal had little effect on shuttle escape performance, acoustic startle and locomotor activity. Based on these findings it was suggested that the development of post-amphetamine depression in the self-stimulation and forced swim paradigms was not related to variations in motoric or arousal mechanisms resulting from amphetamine withdrawal, but rather involved drug-induced changes in motivational processes.

Stressor-provoked response patterns in a swim task: Modification by diazepam

When placed in a water-filled arena in which one area is illuminated mice tend to remain in the illuminated region. Moreover, in a forced-swim task mice initially exhibit vigorous responding followed by a rapid decay of active swimming, and the adoption of a characteristics floating posture. Immediately following exposure to inescapable shock the response invigoration was appreciably enhanced, as was the tendency to remain the illuminated region of the arena. Administration of low doses of diazepam (0.5 and 1.0 mg/kg) prior to testing effectively eliminated the response invigoration, as well as the response of approaching the illuminated region of the arena. It is proposed that the behavioral variations evident soon after uncontrollable shock are related to a transient increase of anxiety or vigilance. Moreover, it is suggested that several time-dependent behavioral variations associated with inescapable shock may be related to alterations of anxiety.

Acute and chronic stress effects on performance in a forced-swim task

The effects of uncontrollable stressors on performance in a subsequent forced-swim paradigm were assessed in mice. Uncontrollable shock initially induced behavioral invigoration; however, within 24 h of stressor application, swimming behavior was depressed relative to nonstressed mice. The controllability of the stressor did not influence the initial invigoration, being present among escapably shocked mice as well as among mice that received (yoked) inescapable shock. In contrast, the depression of responding evident 24 h after stressor application was related to the availability of behavioral coping methods. Finally, following repeated exposure to footshock there was no indication of adaptation to the behavioral changes ordinarily induced by acute shock stress. The data were related to the effects of uncontrollable stressors on escape performance, and with respect to the use of this preparation as an animal model of human depression.