engleski

Interaction of stress and noradrenergic drugs in the control of picrotoxin-induced seizures

The relationship between stress and seizures is not clear. Recent data have shown that acute swim stress lowers the convulsive potency of GABA-related and some GABA-unrelated convulsants (Pericic et al., Epilepsy Res. 43:145-152, 2001). The anticonvulsive effect of swim stress could not be counteracted by the antagonist at benzodiazepine binding sites, flumazenil, by adrenalectomy, or drugs interfering with the synthesis of steroids. On the other hand, it is well known that central noradrenergic neurons are involved in the response and adaptation to stress. The role of noradrenaline in controlling brainstem seizures has also been documented. The aim of this study was to evaluate the possible role of noradrenergic system in the anticonvulsive effect of swim stress in mice. Hence, the mice were prior to stress (10 min swimming at 18-19 0 C) and the i.v. infusion of picrotoxin, pretreated with alpha-methyl-p-tyrosine (alpha-MPT, an inhibitor of catecholamine synthesis), N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, a neurotoxin which destructs noradrenergic axons) or desipramine (a noradrenaline reuptake inhibitor), to test whether the impaired and enhanced noradrenergic transmission respectively, will modify the anticonvulsive effect of swim stress. While in control unstressed animals desipramine (20 mg/kg i.p.) and alpha-MPT (400 mg/kg i.p.) failed to affect the seizure threshold, DSP-4 (50 mg/kg i.p.) had a mild proconvulsant effect. In swim stressed mice neither alpha-MPT nor DSP-4 modified the anticonvulsive effect of stress. Desipramine enhanced the doses of picrotoxin needed to produce running/bouncing clonus, tonic hindlimb extension and death. The results suggest that the noradrenergic system does not play a substantial role in the anticonvulsive effect of swim stess, although an enhanced noradrenergic transmission potentiates this effect.

Stress; Picrotoxin; Convulsions; Desipramine; alpha-Methyl-p-tyrosine (alpha-MPT); N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)

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