Wed, 2013-02-06 11:14 | 
SUMMARY OF THESIS
Crocus Sativus L. is a rare plant, known since antiquity, which is cultivated in countries of the Mediterranean and of central Asia. The dried red stigmas of its flower consist the drug and contain significant amounts of water-soluble carotenoids, known as crocins. Crocins are crocetin glycosides and are considered responsible for the plant’s extensive therapeutic properties.
Various studies have demonstrated crocins’ anti-inflammatory, antioxidant, antitumoral, cardioprotective and antidiabetic properties. Regarding the central nervous system, there is evidence that crocins exhibit remarkable neuroprotective effect [1], act beneficially in learning and memory processes [2] and alleviate symptoms in experimental models of epilepsy [3], Parkinson’s disease [4] and cerebral ischemia [5]. Furthermore clinical studies have revealed their antidepressant effect, which was found to be similar to fluoxetine and imipramine[6-8]. Since it remains unknown if this drug affects other pathophysiological routes of the central nervous system, the aim of the present study was to investigate the possible beneficial action of crocins on experimental models of anxiety, obsessive-compulsive disorder and schizophrenia.
In order to examine the effect of crocins on anxiety we selected the light/dark test, an experimental model which evaluates the anxiolytic action of compounds in rodents and is based on their innate aversion to brightly illuminated areas [9]. The test apparatus is consisted of a plastic box, divided into two equal-size compartments, which communicate by a doorway. One of the compartments is painted black and covered with a lid, while the other is painted white and is illuminated with a 60W light bulb. The rat is placed in the middle of the lit compartment and is allowed to freely explore the box for 5 minutes. Exposure to light causes anxiety to the animal and forces it to seek shelter in the dark compartment. An anxiolytic agent reverses this behavior, leading to a longer remain in the lit compartment.
For the evaluation of crocins’ effects on an experimental model of obsessive-compulsive disorder we shall use m–chlorophenylpiperazine (m-CPP), a serotoninergic 5–ΗΤ2c agonist, which is known to induce excessive self-grooming in rats and exacerbate symptoms in patients with obsessive-compulsive disorder. In order to assess crocins’ actions, an open field test is going to be used, during which the time spent in self-grooming by the animals of each group will be recorded [10].
Finally in order to examine crocins’ efficacy in experimental models of schizophrenia we shall use ketamine, a non-competitive NMDA antagonist, which in subanesthetic dosage produces a psychotomimetic syndrome, characterized by hyperlocomomotion, ataxia, stereotypies, social withdrawal and working memory deficits [11]. To determine crocins’ action against the whole spectrum of symptoms we are going to perform three behavioral techniques: an open field test for the motor disorders, which are considered analogs of positive symptoms of schizophrenia, the social interaction test for the evaluation of social withdrawal, which serves as a model for the negative symptoms and the novel object recognition task for the memory deficits, which mimic the cognitive deficits of patients with schizophrenia.
References
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2: Pitsikas et al. Effects of the active constituents of Crocus sativus L., crocins on recognition and spatial rats' memory. Behav Brain Res. 2007 Nov 2;183(2):141-6.
3: Tamaddonfard et al. Central effect of crocin on penicillin-induced epileptiform activity in rats. Pharmacol Rep. 2012;64(1):94-101.
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5: Zheng et al. Effects and mechanism of Weinaokang on reperfusion-induced vascular injury to cerebral microvessels after global cerebral ischemia. Chin J Integr Med. 2010 Apr; 16(2):145-50.
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7: Akhondzadeh et al. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816]. BMC Complement Altern Med. 2004 Sep 2;4:12.
8: Noorbala et al. Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial. J Ethnopharmacol. 2005 Feb 28; 97(2):281-4.
9: Crawley and Goodwin. Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacol Biochem Behav. 1980 Aug;13(2):167-70.
10: Gráf M. 5-HT2c receptor activation induces grooming behaviour in rats: possible correlations with obsessive-compulsive disorder. Neuropsychopharmacol Hung. 2006 Mar; 8(1):23-8.
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