engleski

Interaction of swim stress and drugs affecting GABAergic transmission

Swim stress is often used as a biological stressor and as an animal model with predictive value for antidepressant drugs. Several groups of authors described the anticonvulsant properties of stress. The effect was not restricted to GABA-related convulsants used in most of these studies, since it was also observed when some GABA-unrelated convulsants were used (Pericic et al., Epilepsy Res. 43: 145-152, 2001). To better understand the role of GABA system in the anticonvulsant effect of stress, in this study the effect of swim stress on the latency to the onset of convulsions produced in mice by two different convulsants, picrotoxin (a non-competitive GABA-A receptor antagonist) and isoniazid (an inhibitor of GABA synthesis), given at different time points in relation to stress, was compared. The latency of isoniazid (400 mg/kg s. c. ) induced convulsions was more prolonged (118 %) when drug was given 10 min before, than when given immediately after (49 %) swim stress (10 min, 22 ° C), while the latency to picrotoxin (3 mg/kg s. c. ) induced convulsions tended to be more enhanced when drug was given immediately after (134 %) than immediately before (103 %) stress. Although isoniazid (200 mg/kg) given 10 min before stress had only a slight effect on stress-induced enhancement of doses of picrotoxin (given by an i. v. infusion 5 min after stress) needed to produce running bouncing clonus, tonic hind limb extension and death, the data might suggest that presynaptic and postsynaptic GABAergic mechanisms are affected by stress. Whether these swim stress induced alterations affect the behavioural effects of benzodiazepines, drugs known to facilitate the effects of GABA, it is not quite clear at present. Therefore the data on the interaction of swim stress and diazepam on the seizure threshold for picrotoxin will also be presented.

swim stress; anticonvulsant activity; isoniazid; diazepam; picrotoxin

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