Estudo dos fatores neuroquímicos associados ao efeito do óleo de peixe sobre parâmetros de recaída em ratos expostos à anfetamina

Abstract

Psychostimulant drugs are widely used all over the world. Among them, amphetamines are prominent which beyond to being used clinically have been used as recreational drugs. Currently, its indiscriminate use with recreational purposes raises many concerns due to its high ability to develop tolerance, positive reinforcement, addiction and relapse. The use of amphetamine drugs is also able to trigger oxidative processes and cellular damage, especially in brain areas rich in dopamine. Thus, the search for alternatives that may favor the treatment of drug addiction and reduce relapse rates become essential, considering the damages caused by this disorder to the individual, family and society. The consumption of omega-3 polyunsaturated fatty acids (PUFA n-3) has shown beneficial influences in the prevention and treatment of various diseases affecting the central nervous system (CNS). The aim of this study was to evaluate the influence of fish oil (FO), rich in PUFA- n3, on behavioral parameters of relapse, as well as its effects on biochemical and molecular markers in rats previously conditioned to amphetamine (AMPH) preference. Wistar rats were separated in two experimental groups: AMPH (4 mg / kg, i.p.) and Vehicle (saline solution - 0.9% NaCl, i.p.) and submitted to the conditioned place preference (CPP) protocol for 14 days. After the CPP test, half of each experimental group was treated orally with FO (3g / kg, p.o.) or water (Control group) for 14 days by gavage. After the treatment/extinction period to the AMPH, the animals that were previously conditioned with the drug were re-exposed to the AMPH/Vehicle for another 3 days and in the sequence the CPP test was again performed. One day after the end of the behavioral evaluations, the animals were euthanized and the prefrontal cortex (PFC) was collected for biochemical and molecular analysis. The results show that treatment with FO reduced the relapse behavior induced by re-conditioning with AMPH. FO, rich in PUFA n-3, increased the incorporation of DHA into the neural membranes of the PFC. In addition, FO treatment was able to protect the CNS against the toxic effects of AMPH by modulating the dopaminergic cascade markers (DAT, TH, VMAT2, D1R and D2R). Furthermore, FO reduced oxidative damage induced by AMPH in the same brain region. In summary, this study provides evidence that an experimental treatment with PUFA n-3 is capable of altering the neurotransmission of the dopaminergic system, reversing the neurotoxic effects caused by the use of AMPH. Thus, this nutraceutical may be an alternative strategy to assist in the treatment of an important public health problem.