Changes In Ensemble Activity Of Hippocampus CA1 Neurons Induced By Chronic Morphine Administration In Freely Behaving Mice

The hippocampus plays an important role in the formation of new memories and spatial navigation. Recently, growing evidence supports the view that it is also involved in addiction to opiates and other drugs. Theoretical and experimental studies suggest that hippocampal neural-network oscillations at specific frequencies and unit firing patterns reflect information of learning and memory encoding. Here, using multichannel recordings from the hippocampal CAl area in behaving mice, we investigated the phase correlations between the theta (4-10 Hz) and gamma (40-100 Hz) oscillations, and the timing of spikes modulated by these oscillations. Local field potentials and single unit recordings in CAl area of mice receiving chronic morphine treatment revealed that the power of the theta rhythm was strongly increased, at the same time, the theta frequency during different behavioral states shifted markedly, and the characteristic coupling of theta and gamma oscillations was altered. Surprisingly, though the gamma oscillation frequency changed, its power did not. Moreover, the timing of pyramidal cell spikes relative to the theta rhythm and the timing of interneuron spikes relative to the gamma rhythm showed change during chronic morphine administration. Furthermore, both responses were dependent on local dopamine receptor activation, since they were impaired by a selective D1/D5 receptor antagonist. These results indicate that changes of ensemble activity in the CAl area caused by chronic morphine administration related to drug addiction.