Drogadição: a estimulação tátil recupera aspectos moleculares e comportamentais associados à recaìda por anfetamina em ratos adultos

Abstract

Drug addiction is a chronic neuropsychiatric disorder characterized by the development of dependence, compulsion and frequent episodes of relapse, as available treatments are ineffective to prevent such a situation. Considering drug addiction, amphetamine (AMPH) exerts a potent psychostimulant action, by acting on dopaminergic receptors such as D1R, a transporter related to dopamine reuptake (DAT), and may also modulate transcription factors such as deltaFosB, with the main effect of increasing dopamine in the synaptic space, which is why it is often used for recreational purposes and is related to drug addiction and relapse.In the search for new therapeutic approaches to treat drug addiction and especially to prevent its recurrence, tactile stimulation (TS) is a technique that arouses interest due to its ability to exert neuroprotection, being beneficial in situations of stress and anxiety at different stages of development. The aim of the present study was to evaluate the influence of TS on drug addiction parameters in adult rats exposed to an AMPH-preference behavioral protocol. Two groups of male Wistar rats (50 days old) were exposed to the conditioned place preference (CPP) paradigm with saline (0.9% NaCl; n=20) or Amphetamine (AMPH - 4.0 mg/Kg; n=20). ) for 8 days. After conditioning and evaluation of drug preference behavior (CPP-1), half of the animals from each experimental group were submitted to the TS protocol, through by handling gently applied to the dorsal surface of the rat in the cranio-sacral direction for 8 days (15 min, 3x/day). From the 9th day, the animals were exposed again to AMPH or saline, for 3 additional days in the CPP to perform the drug relapse test (CPP-2). Working memory and locomotion were monitored in the Y-maze. Afterwards, the animals were euthanized and the nucleus accumbens (NAc) was dissected for molecular analysis by western blot. Behavioral observations showed that animals conditioned with AMPH showed a preference for the drug paired side in CPP-1, while working memory and locomotion showed no difference between the experimental groups, indicating that CPP was due to the hedonic effects of AMPH. It is noteworthy that in addition to preventing the drug relapse, as observed in the CPP-2 test, at the molecular level TS was able to modulate the dopaminergic system, by preventing the increase caused by AMPH in the immunoreactivity of D1 receptors (D1R) of dopamine, the dopamine transporter (DAT), and the enzyme tyrosine hydroxylase (TH). It also exerted this same effect on the transcription factor ΔFosB and on the levels of Mu-opioid receptors (MOR) in the NAc area. Through this study, it was possible to observe that TS was able to exert a neuroprotective influence on NAc, which is an important mesolimbic dopaminergic area of the central nervous system associated with the development and maintenance of drug addiction, preventing drug relapse. Thus, being a non-invasive manipulation and free from adverse effects, it can be inferred that TS can be an adjuvant or complementary therapeutic procedure in the treatment of drug addiction by psychostimulants such as AMPH.