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Objectives: Statins decrease cholesterol synthesis in liver by inhibiting HMG-CoA reductase -the rate controlling enzyme reversibly. Melatonin is a neurotransmitter, which is synthesized from tryptophan and it is released from pineal gland nocturnally. In this study our aim was investigating the effects of atorvastatin and melatonin in experimental psychosis model in rats.
Methods: Forty-two adult male Sprague Dawley rats (220–240 g) were used in the study.
Novelty-induced rearing behavior is assessed. Novelty-induced rearing was evaluated by placing the animals directly from home cages to a transparent Plexiglas cage (45 cm X 25 cm X 25 cm) containing sawdust. All rats were observed and assessed singly in the Plexiglas cage, 7 (n=6) groups of rat were administered atorvastatin (10, 20 mg/kg, i.p.), melatonin (10, 20 mg/kg, i.p.), 1% ethanol sham (1 ml/kg, i.p.) chlorpromazine (1 mg/kg; i.p.) or isotonic NaCl (1 ml/kg, i.p.) Novelty-induced rearing considered as a central excitatory locomotor behavior was counted as the number of times the rat was standing on its hindlimb with its forelimbs against the wall of the observation cage or in the free air. The number of rears was counted for 30 minutes. Apomorphine-induced stereotypic behavior test (n=6) groups of rats were administered atorvastatin (10, 20 mg/kg, i.p.), melatonin (10, 20 mg/kg, i.p.), 1% ethanol sham (1 ml/kg, i.p.) chlorpromazine (1 mg/kg; i.p.) or isotonic NaCl (1 ml/kg, i.p.). One hour later, apomorphine (2 mg/kg s.c.) was administered to each rat. Assessment of stereotyped behavior was done by two observers blind to the study groups. Following apomorphine administration, the rats were immediately placed back into the metal cages and observed for stereotypic behavior. Signs of stereotypy, which include mainly sniffing and gnawing, were observed and scored as follows: absence of stereotypy (0), occasional sniffing (1), occasional sniffing with occasional gnawing (2), frequent gnawing (3), intense continuous gnawing (4), intense gnawing and staying on the same spot (5). The stereotypic behavior was rated after each minute and mean of 15 min period was calculated and recorded.
Results: Comparison of rearing behavior: 20 mg/kg of atorvastatin decreased rearing behavior scores compared to saline group significantly (p<0.05). 20 mg/kg of melatonin decreased rearing behavior scores significantly compared to saline group (p<0.05). Additionally chlorpromazine decreased the rearing behavior scores most (p<0.00001) and 1% ethanol caused a slight increase but did not reach to significant levels (p<0.05) Comparison of stereotypy scores of groups: 10 mg/kgs of atorvastatin group had decreased stereotypy scores compared saline group (p<0.05), but 20 mg/kg of atorvastatin caused a stronger decrease (p<0.001). 10 mg/kg of melatonin did not show significant difference compared to saline group but upon administration of 20 mg/kg of melatonin, stereotypy scores were significantly decreased (p<0.005). Like in rearing behavior scores chlorpromazine caused the most profound decrease in stereotypy scores (p<0.00001), whereas ethanol group showed no difference.
Conclusion: As a conclusion, in this study, we have demonstrated antipsychotic efficacy of melatonin and atorvastatin.