Swimming rats and human depression

Hawkins, James; Hicks, Robert A.; Phillips, Nathan; Moore, John D.

doi:10.1038/274512a0

Cited by 107 publications

(41 citation statements)

References 7 publications

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“…In the original Porsolt swim test, activity was measured in 15 cm of water (Porsolt et al, 1977) which allows animals to stand on the bottom of the swim tank. This results in immobility, the principal behavior these investigators were trying to measure (Porsolt et al, 1977;Hawkins et al, 1978). In contrast, the modification used in this study measured activity in 37.5 cm of water, making it impossible for the animals to rest their feet on the bottom of the tank (Weiss et al, 1986).…”

Section: Discussionmentioning

confidence: 67%

Corticotropin-releasing factor produces fear-enhancing and behavioral activating effects following infusion into the locus coeruleus

et al. 1990

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The present series of experiments tested the hypothesis that the behavioral activating and anxiogenic effects produced by intraventricular administration of corticotropin-releasing factor (CRF) may be mediated by noradrenergic neurons in the brain-stem locus coeruleus (LC). Results showed that infusion of CRF into the LC (100 ng) significantly increased nonambulatory spontaneous motor activity measured in photocell cages; ambulatory (i.e., locomotor) activity was not altered. In the modified Porsolt swim test, which examines arousal and agitation in a stressful situation, significant behavioral activation (i.e., decreased floating) was seen following infusion of CRF (10 ng) into the LC; a 500 ng dose of CRF was necessary to produce similar effects following infusion into the lateral ventricle. The results of these 2 tests suggest that the behavioral activating effects of CRF in the LC may be related to arousing or stress-related effects, rather than to increased locomotor activity per se. Anxiogenic activity was assessed in animals placed in an open field containing a small, darkened compartment. Infusion or CRF into the LC (1–100 ng) significantly increased the time spent in the compartment and decreased the amount of time spent exploring the outside of the compartment or venturing into the inner squares of the open field, all indices of anxiogenic behavior. Biochemical studies showed that bilateral infusion of CRF into the LC produced significant increases in the concentration of the norepinephrine metabolite 3,4-dihydroxyphenylglycol in such forebrain projection areas of the LC as the amygdala and posterior hypothalamus. These data, taken together, suggest that CRF produces its behavioral activating and anxiogenic effects, at least in part, by increasing the activity of LC noradrenergic neurons.

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Section: Discussionmentioning

confidence: 67%

Corticotropin-releasing factor produces fear-enhancing and behavioral activating effects following infusion into the locus coeruleus

et al. 1990

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“…But this alternative explanation is not supported by the finding that antidepressants stimulate glucocorticoid receptor gene expression and the fact that the time course of antidepressant actions on glucocorticoid receptors follows that of clinical improvement of depression (Barden et al, 1995). Alternatively, the immobile posture can be viewed as an energy-conserving strategy (Hawkins et al, 1978;West, 1990). According to this line of reasoning immobility behaviour is a successful passive behavioural strategy.…”

Section: Discussionmentioning

confidence: 99%

Antisense to the glucocorticoid receptor in hippocampal dentate gyrus reduces immobility in forced swim test

Korte

Kloet

Buwalda

et al. 1996

European Journal of Pharmacology

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“…In addition to glucocorticoids, opioids also have been implicated in behavioural performance in this swimming test [15][16][17]. Interaction between opioids and glucocorti coids frequently has been observed during stress in the ex pression of the autonomous, neuroendocrine, behavioural, and immune responses [1,2,20], Such interactions may occur via stress-induced inhibition of opioid peptide syn thesis and release in the pituitary and hypothalamus, and.…”

Section: Discussionmentioning

confidence: 99%

“…The swimming test procedure as described earlier [4,15,[27][28][29] was used. Briefly, the rats were placed individually in narrow glass cylinders (height 25 cm, diameter 18 cm) containing 15 cm of water at 25 °C for 15 min (initial test).…”

Section: Behaviourmentioning

confidence: 99%

Antiglucocorticoid RU 38486 Attenuates Retention of a Behaviour and Disinhibits the Hypothalamic-Pituitary Adrenal Axis at Different Brain Sites

et al. 1988

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Adrenalectomized rats displayed a deficiency in retention of an immobility response acquired during an initial 15-min forced swimming procedure (Porsolt swimming test) and measured 24 h later in a 5-min retest session. The deficit could be restored dose dependently with the glucocorticoid dexamethasone (µg range) administered 15 min after the initial test. The antiglucocorticoid RU 38486 administered subcutaneously (1 and 10 mg/kg) inhibited the dexamethasone effect and caused a parallel shift in the dose-response curve of dexamethasone. Intracerebroventricular administration of RU 38486 to intact rats immediately before the initial test attenuated retention of acquired immobility over a 100,000-fold lower dose range (ng) and increased the plasma corticosterone level. Local administration of 1 ng RU 38486 in the dentate gyrus of the hippocampus also diminished the percentage immobility, but did not influence the adrenocortical response. Injections of RU 38486 in parafascicular and paraventricular nucleus were ineffective on behaviour. In the latter nucleus the antiglucocorticoid disinhibited the activity of the hypothalamus-pituitary-adrenal axis. Intracerebroventricular pretreatment with promegestone did not interfere with RU 38486 action, ruling out involvement of its antiprogestin properties. Intracerebroventricular or subcutaneous treatment of intact rats with the antimineralocorticoid RU 28318 was not effective. Finally, adrenalectomized rats replaced with corticosterone delivered via subcutaneously implanted 100-mg corticosterone pellets showed normal behavioural performance, while a 25-mg implant did not. The present study with local infusions of RU 38486 indicates that glucocorticoid feedback via type 2 receptors exerts a long-term influence on behaviour in the hippocampus and controls the activity of the hypothalamus-pituitary-adrenal axis in the paraventricular nucleus.

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Swimming rats and human depression

Cited by 107 publications

References 7 publications

Corticotropin-releasing factor produces fear-enhancing and behavioral activating effects following infusion into the locus coeruleus

Corticotropin-releasing factor produces fear-enhancing and behavioral activating effects following infusion into the locus coeruleus

Antisense to the glucocorticoid receptor in hippocampal dentate gyrus reduces immobility in forced swim test

Antiglucocorticoid RU 38486 Attenuates Retention of a Behaviour and Disinhibits the Hypothalamic-Pituitary Adrenal Axis at Different Brain Sites

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