Too Much Dopamine And Mouse Awakenings

In Oliver Sack's book "Awakenings," survivors of the 1917-1928 epidemic of encephalitis lethargica temporarily "awaken" from their catatonic state after receiving the then-new drug L-dopa. Although not quite as poetic, Dzirasa et al. tell of another link between dopamine and sleep-wake states. The authors investigated hippocampal local field potentials and electromyographic activity in mice with either genetically or pharmacologically induced changes in dopamine levels. Upon exposure to a novel environment, dopamine transporter - knock-out (DATKO) mice and wild-type mice treated with amphetamine, manipulations resulting in increased extracellular dopamine, exhibited neural activity typical of rapid eye movement (REM) sleep, yet the animals were awake. The D2 receptor antagonist haldol blocked this activity. In contrast, treatment of DAT-KO mice with a tyrosine hydroxylase inhibitor, which completely depleted dopamine stores, abolished REM sleep altogether. These animals exhibited severe Parkinson-like motor symptoms and a novel awake state with oscillations typical of slow-wave sleep.

Kafui Dzirasa, Sidarta Ribeiro, Rui Costa, Lucas M. Santos, Shih-Chieh Lin, Andres Grosmark, Tatyana D. Sotnikova, Raul R. Gainetdinov, Marc G. Caron, and Miguel A. L. Nicolelis

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Too Much Dopamine And Mouse Awakenings