Naslov
Enhancement of serotonergic transmission potentiates the anticonvulsant effect of swim stress in mice

Autori
Peričić, Danka ; Lazić, Josipa ; Jazvinšćak Jembrek, Maja ; Švob Štrac, Dubravka ; Rajčan Špoljarić, Ivana

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts of The Fourth Croatian Congress of Pharmacology with international participation ; u: Periodicum biologorum 106 (2004) (S1) / Vitale, Branko - Zagreb, 2004, 91-91

Skup
Croatian Congress of Pharmacology with international participation (4 ; 2004)

Mjesto i datum
Split, Hrvatska, 15.09.2004. - 18.09.2004

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
stress; picrotoxin; convulsions; fluoxetine; zimelidine; pCPA

Sažetak
Although our thoughts on stress implicate primarily the consideration of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathoadrenal system, it is known that many central neuronal systems, including serotonergic (5-HT), are sensitive to stressors. Both, serotonin and stress have been implicated in affective disorders, especially depression, and swim stress is often used as a biological stressor and as an animal model with predictive value for antidepressant drugs. The aim of this study was to assess whether drugs that modify serotonergic transmission affect previously observed (Peričić et al., Psychopharmacology 158: 87-93, 2001) anticonvulsant effect of swim stress in mice. Male CBA mice were prior to exposure to stress (10-min swimming at 18-19 °C) and the i.v. infusion (starting 15 min after termination of stress) of picrotoxin, a non-competitive GABAA receptor antagonist, pre-treated with selective serotonin reuptake inhibitors, zimelidine and fluoxetine (10 and 20 mg/kg i.p. 40 min prior to stress). The seizure threshold for picrotoxin in stressed and unstressed mice was also studied after repeated fluoxetine (20 mg/kg once daily for 5 consecutive days) treatment, and after depletion of serotonin with parachlorophenylalanine (pCPA, 300 mg/kg i.p. given for 3 days), an inhibitor of serotonin synthesis. Doses of picrotoxin needed to produce running bouncing (RB) clonus, tonic hindlimb extension (THE) and death were calculated from the latency to the onset of these convulsant signs. In accordance with our results published previously (Peričić et al., Psychopharmacology 158: 87-93, 2001) swim stress enhanced markedly the doses of picrotoxin needed to produce RB clonus, THE and death. Administration of zimelidine and fluoxetine, two drugs supposed to enhance serotonergic transmission, showed differences in the effect on the seizure threshold for picrotoxin. Zimelidine (20 mg/kg) enhanced in swim-stressed, but not in unstressed animals the doses of picrotoxin producing RB clonus, THE and death. On the other hand, acute and repeated fluoxetine treatment enhanced the seizure threshold for picrotoxin in unstressed and swim stressed mice. Serotonin depletion following pCPA treatment failed to affect doses of picrotoxin needed to produce convulsant signs and death. The results of the present work have confirmed and extended the data of our previous studies demonstrating a pronounced anticonvulsant effect of swim stress. Further, the study suggests that drugs that enhance serotonergic transmission, potentiate the anticonvulsant effect of swim stress against convulsions induced by picrotoxin, a non-competitive GABAA receptor antagonist. Differences in the effect of two selective serotonin reuptake inhibitors on the seizure threshold for picrotoxin in unstressed animals are not clear at present. A lack of effect of serotonin depletion by pCPA on the seizure threshold for picrotoxin and death suggests that the presynaptic 5-HT stores are not important for the control of picrotoxin-induced seizures. While zimelidine enhanced the seizure threshold for picrotoxin only in swim-stressed mice, both acute and repeated fluoxetine treatment, enhanced the seizure threshold for picrotoxin in unstressed animals as well.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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