Memory improving and antidepressant effects of topiramate in rats.
Topiramate (TOP, CAS 97240-79-4) particularly potentiates gamma-aminobutyric acid (GABA) neuroinhibition, and GABA and glutamate receptors, which have also been implicated in memory formation. Patients' giving up treatment due to adverse effects (disorders of attention, memory, and verbal fluency) is the main problem with a therapy based on this drug. The antidepressant effect of TOP administered to rats in the dose of 15 mg/kg is observed only after 14 and 21 days of treatment. The delay in the antidepressant effect of TOP may be due to the modulation of GABA A receptors as well as due to the influence of the drug on receptors for type AMPA/KAIN excitatory amino acids. The research has also shown that long-term treatment with TOP in a dose of 15 mg/kg improved spatial memory, as tested in rats with Morris test. Probably, this results from the influence of the drug on GABA A receptors and the function of glutaminergic receptors (especially in processes like coding, retrieving, and potentiation of information), adaptive processes in the brain, notwithstanding, being an important factor. As TOP is a normothymic drug, its use in the treatment of epilepsy may also positively influence cognitive processes in the so-called interseizure intervals with memory disorders; the same effects can be expected in the treatments of bipolar disorder.
Nowakowska
Elzbieta
E
Department of Pharmacoeconomics and Social Pharmacy, Karol Marcinkowski University of Medical Sciences, Poznan, Poland. elapharm@ump.edu.pl
Kus
Krzysztof
K
Czubak
Anna
A
Jedrzejewska
Joanna
J
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000928:Antidepressive Agents; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming / Q000523:psychology; D000077236:Topiramate
D000927:Anticonvulsants; D000928:Antidepressive Agents; D000077236:Topiramate; D005632:Fructose