¹Department of Medical Pharmacology, Psychopharmacology Research Unit, Gulhane Military Medical Academy, Ankara, Turkey

Correspondence: Professor TI Uzbay, Department of Medical Pharmacology, Psychopharmacology Research Unit, Gulhane Military Medical Academy, Etlik, 06018 Ankara, Turkey. Tel: +90 312 304 4764; Fax: +90 312 304 2010; E-mail: tuzbay@gata.edu.tr

Received 17 February 2006; Revised 22 May 2006; Accepted 25 May 2006; Published online 28 June 2006.

Abstract

Depression is a common psychiatric problem in epileptic patients. Thus, it is important that an antidepressant agent has anticonvulsant activity. This study was organized to investigate the effects of tianeptine, an atypical antidepressant, on pentylenetetrazole (PTZ)-induced seizure in mice. A possible contribution of adenosine receptors was also evaluated. Adult male Swiss–Webster mice (25–35 g) were subjects. PTZ (80 mg/kg, i.p.) was injected to mice 30 min after tianeptine (2.5–80 mg/kg, i.p.) or saline administration. The onset times of 'first myoclonic jerk' (FMJ) and 'generalized clonic seizures' (GCS) were recorded. Duration of 600 s was taken as a cutoff time in calculation of the onset time of the seizures. To evaluate the contribution of adenosine receptors in the effect of tianeptine, a nonspecific adenosine receptor antagonist caffeine, a specific A₁ receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a specific A2_A receptor antagonist 8-(3-chlorostyryl) caffeine (CSC) or their vehicles were administered to the mice 15 min before tianeptine (80 mg/kg) or saline treatments. Tianeptine (40 and 80 mg/kg) pretreatment significantly delayed the onset time of FMJ and GCS. Caffeine (10–60 mg/kg, i.p.) dose-dependently blocked the retarding effect of tianeptine (80 mg/kg) on the onset times of FMJ and GCS. DPCPX (20 mg/kg) but not CSC (1–8 mg/kg) blocked the effect of tianeptine (80 mg/kg) on FMJ. Our results suggest that tianeptine delayed the onset time of PTZ-induced seizures via adenosine A₁ receptors in mice. Thus, this drug may be a useful choice for epileptic patients with depression.