Alterações comportamentais e neuroquímicas provocadas por diferentes períodos de retirada após tratamento subcrônico com cocaína em ratos : envolvimento dos sistemas dopaminérgico, serotonérgico e noradrenérgico

Abstract

Cocaine is world used and considered as a public health problem, being the relapse one of the hardly difficulties faced by cocaine users, that in the most cases, is related to abstinence symptoms, like anxiety, depression, irritability, fatigue and sleeplessness. To evaluate the behavioral alterations (anxiety and depression) and neurochemistry, rats were submitted to 24h, 7 d and 21 d withdrawal, after the subcronic treatment, for 7 days with cocaine (20mg/kg), being realized the experimental models of Elevated Plus Maze (EPM), Open Field (OF) and Forced Swimming (FS). Moreover, in the 24h abstinence, propranolol (10mg/kg, i.p.), ondansetrom (4mg/kg, i.p) and buspirone (5 mg/kg, i.p.) had been tested, in the EPM and OF, as wel as in the 21 d of abstinence bupropione (30mg/kg, i.p.) and paroxetine (10 mg/kg, i.p.) had been tested in the FS, aiming to revert the alterations caused by the abstinence of cocaine subcronic administration. For the neurochemistry study (neuroadaptation) was used striatum (ST) of rats, evaluating the following parameters: level of monoamines (NE, DA and 5HT) and its metabolites (DOPAC, HVA and 5HIAA), using the electrochemistry detection HPLC and the activity of the catalase enzyme. In the anxiety evaluation, results showed that in the EPM there was a reduction on NEOA, PEOA, TPOA and PTOA in the abstinence of 24h, 7 d and 21 d. In the OF, the withdrawal of 24 and 7 d promoted an increasing in the locomotor activity of animals, while the withdrawal of 21 d a decreasing in the locomotor activity was observed. In the 24h abstinence were administered propranolol, ondansetrom and buspirone. In the EPM, propranolol increased NEOA and reduced PTOA, while ondansetrom increased NEOA, PEOA, TPOA and PTOA, as compared to cocaine group. In addition buspirone as compared to cocaine group increased PTOA, TPOA, and PEOA, however NEOA was reduced. While in the OF, propranolol, ondansetron and buspirone reduced the locomotor activity as related to cocaine group. To evaluate the antidepressive effect the FS was performed, where the withdrawal of 24h and 7 d reduced the immobility time, although in the 21 d abstinence an increase of this parameter was observed. In the 21 d abstinence had been administered paroxetine and buproprione, verifying a reduction of the immobility time as related to cocaine group. To the performance of neurochemistry studies, animals were dissected to take off the ST. In the ST was observed an increasing of dopamine (DA) and a reduction of its metabolites (DOPAC and HVA) in the three withdrawals. The serotonine levels increased the three withdrawals, however its metabolite (5HIAA) increased only in the 24h and 7 d withdrawals. In addition norepinephrine reduced after the 24h, 7 d and 21 d withdrawal. In relation to the receptors, in the ST D2 24h and 7d met high in, already 5HT2 after 7d and D1 was not alteration. Were evaluated too in the ST the activity of catalase, antioxidant enzyme, that showed a reduction of your activity in the three withdrawal. Results suggests that different times of withdrawal after subcronic treatment with cocaine cause anxyogenic and depressive effects on the CNS and this effects were reverted by the administration of drugs (propranolol, ondansetrom, buspirone, bupropione and paroxetine). The neurochemistry study showed that the abstinence of cocaine were events multimediated and the brain area study ST has an important role, being the catalase activity involved in this process. These findings are important to the investigation of new treatments to the cocaine abstinence syndrome.