title: Interaction of stress and noradrenergic drugs in the control of picrotoxin-induced seizures.
abstract: 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.
mesh_terms: 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
chemical_list: 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