Swim stress alters the behavioural response of mice to GABA-related and some GABA-unrelated convulsants
Introduction
Recent data have demonstrated that swim stress attenuates in a sex-dependent manner the convulsive potency of bicuculline (Pericic and Bujas, 1997), a competitive antagonist of GABA binding sites. These results have supported other studies which have shown that stressful manipulations in rats decrease convulsant potency of bicuculline (Drugan et al., 1985), picrotoxin and pentylenetetrazole (Soubrie et al., 1980, Abel and Berman, 1993), as well as the studies suggesting an augmented function of the brain GABA system following acute swim stress (Skerritt et al., 1981, Schwartz et al., 1987, Akinci and Johnston, 1993, Akinci and Johnston, 1997). An increase in benzodiazepine binding sites (Motohashi et al., 1993, Wilson and Biscardi, 1994) and elevations of GABAA receptor active steroids in the brain (Purdy et al., 1991) following the same stressful procedure have also been described. In some of these studies, the authors have shown that stress or control over stress do not affect the convulsions induced by GABA-unrelated convulsants, e.g., strychnine (Soubrie et al., 1980, Drugan et al., 1994).
However, the effect of stress on the convulsive activity produced by convulsants with different mechanism of action, has not been systematically studied. It is also not clear whether cold or exercise are responsible for the observed swim stress-induced alterations of the behavioural response to convulsants, as well as whether repeated exposure to a stressor produces tolerance to the observed effects.
Hence, the aim of this study was to evaluate whether previously observed swim stress-induced changes in the activity of convulsants are as a result of the activation of the GABA system restricted only to GABA-related convulsants or whether it is a more general phenomenon which includes the activation of another inhibitory neurotransmitter system (glycine) and/or the inhibition of the main excitatory neurotransmitter system. Further, we compared the effect of swimming in cold (18–19°C) with the swimming at room temperature, and the effect of repeated with the effect of single stress on the convulsions produced by picrotoxin, a non-competitive GABAA receptor antagonist.
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Animals
Male CBA mice (25–30 g) bred in our institute, three months old, were used. They were housed at a constant temperature (22°C) and with a light cycle of 12 h light/12 h darkness (lights on at 7.00 a.m.). They were caged in groups of 10. Food and water were freely available. Prior to experiment, the animals were not habituated to i.v. drug administration. All animal procedures were carried out in accordance with the ‘Principles of laboratory animal care’ (NIH publication no. 85-23, revised 1985)
Results
As shown in Fig. 1A, in accordance with our results obtained on rats (Pericic and Bujas, 1997), swim stress enhanced significantly (P<0.001, Student's t-test, N=7–9 animals per group) the doses of bicuculline (a competitive GABAA receptor antagonist) producing all convulsant signs: myoclonus, writhe, RB clonus and THE. The enhancements ranged 36–46%. The dose of bicuculline needed to produce death was also enhanced (43% when compared with the dose in unstressed group).
As shown in Fig. 1B, swim
Discussion
In accordance with some previous studies, the results presented in this paper demonstrate that swim stress lowers the activity of GABA-related (bicuculline, picrotoxin, pentylenetetrazole) and two GABA-unrelated (strychnine, 4-aminopyridine) convulsants, but it does not affect the convulsant potency of kainic acid, an excitatory amino acid agonist selective for the kainate receptor subtype (Chittajallu et al., 1999).
Among the GABA related convulsants, swim stress was the most effective against
Acknowledgements
This study was supported by the Croatian Ministry of Science and Technology. The skilful technical assistance of Mrs. Zlatica Tonšetic is gratefully acknowledged.
References (35)
- et al.
Sex differences in the effects of gonadectomy and acute swim stress on GABAA receptor binding in mouse forebrain membranes
Neurochem. Int.
(1997) - et al.
Stress and β-carbolines decrease the density of low affinity GABA binding sites. An effect reversed by diazepam
Brain Res.
(1984) - et al.
Kainate receptors: subunits, synaptic localisation and function
Trends Pharmacol. Sci.
(1999) - et al.
Central serotonin depletion modulates the behavioural, endocrine and physiological responses to repeated social stress and subsequent C-fos expression in the brains of male rats
Neuroscience
(1999) - et al.
Effects of cold-restraint and swim stress on convulsions induced by pentylentetrazol and electroshock: influence of naloxone pre-treatment
Pharmacol. Biochem. Behav.
(1991) - et al.
The protective effects of stress control may be mediated by increased brain levels of benzodiazepine receptor agonists
Brain Res.
(1994) - et al.
Coping and seizure susceptibility: control over shock protects against bicuculline-induced seizures
Brain Res.
(1985) - et al.
Stress-induced behavioural depression in the rat is associated with a decrease in GABA receptor-mediated chloride ion flux and brain benzodiazepine receptor occupancy
Brain Res.
(1989) - et al.
The behavioural and neuronal effects of the chronic administration of benzodiazepine anxiolytic and hypnotic drugs
Progr. Neurobiol.
(1996) - et al.
Genetic correlations among inbred strain sensitivities to convulsions induced by 9 convulsant drugs
Brain Res.
(1990)
The habituation of brainstem catecholaminergic groups to chronic daily restraint stress is stress specific like that of the hypothalamo-pituitary-adrenal axis
Brain Res.
Effects of single and repeated stresses on the expression of mRNA for alpha(1)-adrenoceptors in the rat hypothalamus and midbrain
Eur. J. Pharmacol.
Acute swim stress increases benzodiazepine receptors, but not GABAA or GABAB receptors, in the rat cerebral cortex
Neurochem. Int.
Sex differences in bicuculline-induced convulsions: interaction with stress and ligands of benzodiazepine binding sites
Brain Res.
Acute stress enhances the activity of the GABA receptor-gated chloride ion channel in brain
Brain Res.
The response pattern of noradrenaline release to repeated stress in the hypothalamic paraventricular nucleus differs according to the form of stress in rats
Brain Res.
Increased GABA binding in mouse brain following acute swim stress
Brain Res.
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2012, Brain ResearchCitation Excerpt :For instance, Schmidt et al. (2003) demonstrated that the stress response system of early postnatal animals was less responsive to stresses, that is, the system was not fully functioning. Recent studies using adult animals have shown the effects of swim stress, the most widely used stressor, on the convulsion threshold with convulsant drugs including pentylenetetrazol (PTZ) (Fournier et al., 2008; Peričić and Švob, 2001; Peričić et al., 2001, 2007; Reddy and Rogawski, 2002). Swim stress at room temperature for 10 min, not restraint and nociception stress, delayed the onset time of convulsion produced by pilocarpine in rats (Fournier et al., 2008).