Other Approaches

In the future, it may be possible to modulate brain glutamate systems by treatments that are designed to modify the expression of critical genes involved in glutamate signaling. Indeed, drugs of abuse produce prominent changes in gene transcription that may alter the expression of components of the glutamate-signaling pathways and these changes have been hypothesized to play a role in the development of drug dependence (193). Furthermore, drugs used to treat drug dependence may also operate through similar pathways. For example, antidepressants, widely used to treat drug dependence (3), appear to have the common effect of increasing the levels of growth factors such as brain-derived neurotrophic factor (BDNF), as pointed out by Skolnick (194). Depression is comorbid with drug-dependence syndromes (195) and NMDA-receptor antagonists are effective in animal models of depression (194), as they are in models of drug addiction. Therefore, novel approaches to the treatment of drug addiction may be based on the design of compounds that promote BDNF formation as, for example, through the cyclic AMP-dependent response pathway. Increased levels of BDNF could then ultimately result in a dampending of NMDA receptor function through the regulation of NMDA receptor genes (cf. ref. 195).

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