Elsevier

Epilepsy Research

Volume 43, Issue 2, February 2001, Pages 145-152
Epilepsy Research

Swim stress alters the behavioural response of mice to GABA-related and some GABA-unrelated convulsants

https://doi.org/10.1016/S0920-1211(00)00194-7Get rights and content

Abstract

To elucidate the relationship between stress and seizures, the effect of a single swim stress on the convulsive signs and death produced by several GABA-related and GABA-unrelated convulsants, and the effect of repeated swim stress on picrotoxin-induced convulsions was studied. Mice were subjected to swim stress (10 min swimming at 18–19°C), and the i.v. infusion of convulsants started 15 min thereafter. The latency to the onset of several convulsant signs and death was measured, and the doses of convulsants producing convulsions and death were calculated. Additional experiments included mice swimming at room temperature, and those which were stressed repeatedly (twice a day for four consecutive days, plus one stressful procedure on the fifth day). Swim stress increased the dose needed to produce convulsant signs and death after bicuculline, picrotoxin, pentylenetetrazole, strychnine and 4-aminopyridine, while kainic acid-induced convulsions were not affected. Using picrotoxin infusion, the effect of swimming in room temperature water was less than the effect of swimming in 18–19°C water. In addition, the effect of repeated stress was less than the effect of acute stress on picrotoxin-induced convulsions. The results demonstrate that acute swim stress lowers the convulsive potency of GABA-related and some GABA-unrelated convulsants. Repeatedly stressed animals develop tolerance to anticonvulsive effect of swim stress.

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)

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    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).

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