Interaction of stress and noradrenergic drugs in the control of picrotoxin-induced seizures.
To evaluate the possible role of noradrenergic system in the anticonvulsant effect of swim stress, the mice were prior to exposure to swim stress and the i.v. infusion of picrotoxin, pre-treated with desipramine (a noradrenaline reuptake inhibitor), N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, a neurotoxin which destructs noradrenergic axons) or alpha-methyl-p-tyrosine (alpha-MPT, an inhibitor of catecholamine synthesis) and the latency to the onset of two convulsant signs and death was registered. While in control unstressed animals desipramine (20 mg/kg i.p.) and alpha-MPT (200 mg/kg i.p.) failed to affect, DSP-4 (50 mg/kg i.p., given 3 weeks prior to experiment) tended to decrease the dose of picrotoxin needed to produce tonic hindlimb extension (THE) and death. Swim stress prolonged the latency, i.e. increased (64-116% above control) the dose of picrotoxin needed to produce convulsant signs and death. In swim stressed mice desipramine enhanced the doses of picrotoxin needed to produce running-bouncing clonus (RB clonus), THE and death. alpha-MPT and DSP-4 pre-treatment failed to prevent the anticonvulsant effect of stress. Moreover, the effect of stress was greater in DSP-4 pre-treated mice. Although further studies are needed, the results suggest that the integrity of noradrenergic system is not substantial for the anticonvulsant effect of stress.
D018663:Adrenergic Agents / Q000627:therapeutic use*; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D001596:Benzylamines / Q000633:toxicity; D003891:Desipramine / Q000627:therapeutic use; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D018756:GABA Antagonists; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010852:Picrotoxin; D012640:Seizures / Q000139:chemically induced / Q000150:complications / Q000401:mortality / Q000517:prevention & control*; D013312:Stress, Physiological / Q000150:complications*; D013550:Swimming; D019805:alpha-Methyltyrosine / Q000627:therapeutic use
D018663:Adrenergic Agents; D018759:Adrenergic Uptake Inhibitors; D001596:Benzylamines; D003891:Desipramine; D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D010852:Picrotoxin; D019805:alpha-Methyltyrosine; C012102:DSP 4