Effect of combined treatment with nandrolone and cocaine on the NMDA receptor gene expression in the rat nucleus accumbens and periaqueductal gray

Objective: Anabolic androgenic steroids (AAS) have been suggested to sensitize mechanisms involved in drug dependency and aggressive behaviour. Nucleus accumbens and periaqueductal gray (PAG) are believed to be critical in the functional anatomy of these two phenomena, which are partly mediated by the NMDA receptor. This study was undertaken in order to determine the relationship between the effect of AAS and cocaine (given alone or in combination) on the gene expression of the NMDA receptor subtype NR1 in the rat nucleus accumbens and PAG. Method: Male rats were subjected to 2 weeks of daily doses of cocaine and the anabolic-androgenic steroid nandrolone, administrated separately or in combination, and the effect on the mRNA expression for the NMDA receptor NR1 subunit was studied by Northern blot analysis. Results: In the nucleus accumbens, injection of cocaine alone and the combination of cocaine and nandrolone caused a significant decrease in the NR1 mRNA level compared with that of control rats. The combined treatment significantly down-regulated the transcript in the PAG compared with the groups injected with vehicle, nandrolone or cocaine alone. Conclusion: It was concluded that AAS combined with cocaine may induce additive increases in glutamatergic activity in these brain areas, supporting the notion that these steroids can sensitize mechanisms involved in the reward and the expression of aggression.