Anabolic-androgenic steroids (AAS) are synthetic derivatives of Testosterone which are abused at supraphysiological doses by athletes and adolescent as performance enhancer or for cosmetic purposes. It has been reported that, especially in adolescent, the chronic abuse of anabolic steroids leads to several side effects such as: depression, suicide tendencies, early on-set schizophrenia, aggression and increased violence. However, the mechanisms by which AASs modulate brains activity are still unknown and therapeutic strategies to fight AASs abuse and side effects are missing. By using electrophysiological and behavioral approaches the goal of this project is to describe the effect of high doses of AASs in the Ventral Tegmental Area(VTA). As a matter of facts, dopamine neurons of VTA have been described as on the main target of all drugs of abuse and are involved in the modulation and development of drug addiction, aggression, depression and schizophrenia. Our preliminary data shown that treatment with high doses of the synthetic steroid Nandrolone induces potentiation of glutamatergic transmission on dopamine neurons of the VTA. The effect of Nandrolone is not mediated by the intracellular androgen receptor but requires the activation of mu-opioids receptor probably due to the release of endogenous opioids such as beta-endorphin. This finding could unmask an unexpected target of AAS which could explain the rewarding properties of acute treatment with androgens and the development of AASs side effects after chronic abuse. Future studies will be carry on in order to dissect the link between androgens and the endogenous opioid system focusing on the initial rewarding properties of AAS and the consequent neuro-adaptation occurring after prolonged abuse of AAS.
| Tejeda, Hugo A; Wu, Jocelyn; Kornspun, Alana R et al. (2017) Pathway- and Cell-Specific Kappa-Opioid Receptor Modulation of Excitation-Inhibition Balance Differentially Gates D1 and D2 Accumbens Neuron Activity. Neuron 93:147-163 |
