Effects of the ACTH4-9 analog Org2766 on brain plasticity: modulation of excitatory neurotransmission?

ACTH-like neuropeptides have been investigated in various paradigms such as cognition, neuronal damage and neuronal excitation. All their effects may be collectively described as modulation of neural plasticity. However, the mechanism of action accounting for these effects remains to be demonstrated. This report is an overview of the data and has incorporated some additional findings of the influence of the ACTH4-9 analog, Org2766, on neuronal excitation, especially in the hippocampus. An interaction with NMDA receptors may account for the various aspects of plasticity. Based on recent findings demonstrating that the ACTH4-9 analog counteracts both the NMDA antagonist, AP5, and NMDA-induced explosive running behavior, the hypothesis is put forward that glutamatergic neurotransmission is involved in behavioral changes induced by the ACTH4-9 analog.