engleski

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

The aim of this study was to assess whether drugs affecting serotonergic transmission have an effect on swim stress induced changes of the behaviour reflecting the activity of the brain GABA system. Male CBA mice were, prior to exposure to stress (10-min swimming at 18-19°C) and the i.v. infusion of picrotoxin (starting 15 min after termination of stress), pre-treated with zimelidine (a selective serotonin reuptake inhibitor), 1-(2, 5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI, a selective 5-HT2 receptor agonist) or (± ; ; )-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT, a specific 5-HT1 receptor agonist). Results and Conclusions: In accordance with our previous results (Pericic et al., Psychopharmacology 2001), swim stress enhanced markedly the doses of picrotoxin needed to produce running bouncing (RB) clonus, tonic hindlimb extension (THE) and death. Zimelidine (20 mg/kg i.p., 40 min prior to stress) enhanced in swim-stressed, but not in unstressed animals the doses of picrotoxin producing RB clonus, THE and death. Analogous effects were obtained by 8-OH-DPAT (1 mg/kg i.p. 40 min before stress). DOI (2.5 mg/kg i.p. given immediately before stress) failed to affect in unstressed and swim-stressed mice doses of picrotoxin needed to produce convulsant symptoms and death. These results confirmed and extended the data of our previous studies demonstrating the anticonvulsant effect of swim stress. They further suggest that zimelidine potentiates the anticonvulsant effect of swim stress, presumably by stimulating 5-HT1A receptors. Along with our previous data demonstrating that swim stress inhibits 5-HT2A receptor-mediated behaviour in mice (Pericic, Psychopharmacology 2003), the present data suggest that 5-HT2 receptors do not appear to play a significant role in the anticonvulsant effect of swim stress.

Stress; Serotonergic drugs; Seizures; Picrotoxin

DOI: 10.1111/j.1472-8206.2004.00260.x