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Anticonvulsant effect of aqueous extract of Valeriana officinalis in amygdala-kindled rats: Possible involvement of adenosine

Valerian (Valeriana officinalis L., Valerianaceae) extracts have been used extensively for the treatment of insomnia worldwide. Considerable evidences exist for anxiolytic and sedative effects of valerian both in humans and animals (Houghton, 1999). Furthermore, valerian root has been used as a rather popular anticonvulsant remedy in Europe and Iran in the past centuries (Gorji and Khaleghi Ghadiri, 2001; Eadie, 2004). The anticonvulsive effects of valerian have been evaluated in limited number of studies. The ethanol extract of valerian has been reported to be effective against picrotoxin but not pentylenetetrazole-induced convulsions (Hiller and Zetler, 1996). However, Petkov and Manolov (1975) reported that valerian could antagonize convulsions induced by pentylenetetrazole and strychnine in mice.

Temporal lobe epilepsy (TLE) is the most common epileptic syndrome in adults, as well as the most difficult to manage (French et al., 1993). Kindling is one of the most commonly used animal models of temporal lobe epilepsy which has been used for preclinical evaluation of antiepileptic drugs (Sato et al., 1990). Kindling is defined as progressive development of electrographic and motor seizures after repeated daily stimulation of particular brain sites (Goddard et al., 1969). The amygdala is an important structure in the brain that is involved in the development of complex partial seizures (Gonc¸ alves Pereira et al., 2005).

Despite intensive research efforts, the pharmacological actions accounting for the CNS suppressant effect of valerian remain unclear. Although this effect is believed to be mediated mainly through GABAergic system (Mennini et al., 1993), the involvement of other mechanisms cannot be excluded. Some studies have shown that serotonin (Dietz et al., 2005), melatonin (Abourashed et al., 2004) or adenosine (Lacher et al., 2007) could be involved in the valerian mediated sedation and anxiolysis. The interaction of valerian extract with adenosine system has been the subject of some recent studies. In these studies, the existence of compounds with partial agonistic or inverse agonistic activity on A1 adenosine receptors in different valerian extracts has been reported (Lacher et al., 2007; Sichardt et al., 2007).