Estudo ontogênico do efeito agudo do metilfenidato em camundongos submetidos ao modelo de convulsão induzida por Pilocarpina

Abstract

Attention-deficit hyperactivity disorder (ADHD) is a prevalent and debilitating disorder diagnosed on the basis in persistent levels of overactivity, inattention and impulsivity. Stimulant drugs have been effective in treating this disorder, and methylphenidate (MPH) is the most widely prescribed therapeutic agent and its use has increased significantly in recent years, however, the consequences of its use are still poorly known. Some studies have inferred that the MPH can develop epilepsy or exacerbate seizures in children with epilepsy already established. In this sense, this project aimed to study the effects of acute administration of methylphenidate on the central nervous system in young and adult animals through pilocarpine-induced seizures and determination of enzyme activity acetylcholinesterase (AChE). The MPH was administered acutely at doses of 2.5; 5; 10 and 20 mg / kg, via the oral route, and after 60 minutes pilocarpine 400mg/kg (P400) was administered intraperitoneally. After the seizure test, brain areas (hippocampus and striatum) were dissected for determination of AChE activity. The pilocarpine-induced seizures results showed that methylphenidate decreased seizure latency in young animals [MPH5: 423,825,63 (p<0,05); MPH10: 378,222,41 (p<0,01); MPH20: 357,225,28 (p<0,001); P400: 538,739,63] and adult [MPH2,5: 564,344,76 (p<0,001); MPH5: 632,346,90 (p<0,01); MPH10: 677,943,54 (p<0,01); MPH20: 696,025,99 (p<0,01); P400: 875,742,80], as well decreased the percentage of survival in young animals [MPH 2,5; 5; 10; 20: 0%; P400: 23,1%] and adult [MPH 2,5; 5; 10; 20: 0%; P400: 35,72%]. The study of the effects of the cholinergic neurotransmission system has show that pretreatment with MPH reduced AChE activity only in the striatum, in young animals [CTRL: 83,54±5,14; MPH5: 57,40±6,43 (p<0,05); MPH10: 43,03±7,60 (p<0,001); MPH20: 59,38±5,54 (p<0,05)] and adult [CTRL: 141,8±12,71; MPH2,5: 64,48±4,34 (p<0,001); MPH5: 56,50±5,30 (p<0,001)]. In conclusion, our findings suggest that the MPH displays proconvulsivante effect through the modulation of the muscarinic cholinergic system as a mechanism for augmentation of seizures.