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Heroin Addiction and Related Clinical Problems: 2017, 19, N5 (pages: 73 - 78)

Effects of Naltrexone Treatment on Hypothalamic-Pituitary-Adrenal Axis Activation and Gaba Release in Rats

Stella L., Oliva P., Boccella S., Scafuro M.A., Giordano C., Scala G., Guida F., Leone A., Marabese I., and de Novellis V.

Summary: Background: Narcotic antagonists, such as naltrexone (NTX), are effective not only in the treatment of opiate addiction, but also of alcohol dependency. Repeated treatment with NTX is, however, associated with several side-effects, including insomnia, anxiety, panic attacks and ‘hyperexcitability', which are often responsible for treatment withdrawal. Previous findings reported that such behavioural alterations are associated with changes in GABA levels in the brain that are responsible for an overactivated hypothalamic-pituitary-adrenal axis. Aim: The aim of this study has been to evaluate the effect of the benzodiazepine prazepam on the biochemical changes induced by NTX treatment. Materials and Methods: We have evaluated GABA levels following NTX treatment alone or in presence of prazepam in three brain regions (globus pallidus, posterior hypothalamus and hippocampus) in freely moving rats. In addition, the concentrations of ACTH and corticosterone have been measured. Results: Acute or chronic NTX treatment reduced extracellular GABA levels in the brain and increased blood concentrations of ACTH and corticosterone in a dose-dependent manner. Prazepam (PRZ) administered prior to treatment significantly prevented these effects. Conclusions: This study demonstrates that PRZ is able to prevent the biochemical changes believed to be associated with NTX-induced behavioural changes. Moreover, our data suggest the use of NTX combined with PRZ as a new pharmacological tool in the treatment of patients addicted to opioids.