Abstract
Cortical neurons oscillate between Up and Down states during slow wave sleep and general anesthesia. Recent studies show that Up/Down oscillations also occur during quiet wakefulness. Arousal eliminates Down states and transforms Up/Down oscillations to a persistent Up state. Further evidence suggests that Up/Down oscillations are crucial to memory consolidation, whereas their transition to a persistent Up state is essential for arousal and attention. We have shown that D-amphetamine promotes cortical Up state, and the effect depends on activation of central α1A adrenergic receptors. Here, we report that dopamine also plays a role in D-amphetamine’s effect. Thus, using local-field-potential recording in the prefrontal cortex in chloral hydrate-anesthetized rats, we showed that the Up-state promoting effect of D-amphetamine was attenuated by antagonists at either D1 or D2-like dopamine receptors. The effect was also partially mimicked by co-activation of D1 and D2-like receptors. These results are consistent with the fact that D-amphetamine increases the release of both norepinephrine and dopamine. They are also in agreement with studies showing that dopamine promotes wakefulness and mediates D-amphetamine-induced emergence from general anesthesia. The effect of D-amphetamine was not mimicked, however, by activation of either D1 or D2-like receptors alone, indicating an interdependence between D1 and D2-like receptors. The dopamine/norepinephrine precursor L-DOPA also failed to promote the Up state. While more studies are needed to understand the difference between L-DOPA and D-amphetamine, our finding may provide an explanation for why L-DOPA lacks significant psychostimulant properties and is ineffective in treating attention-deficit/hyperactivity disorder.
Highlights
During slow wave sleep and general anesthesia, the membrane potential of cortical neurons alternates between two preferred levels known as the Up and Down states (Neske, 2016; Poulet and Crochet, 2019)
In chloral hydrate-anesthetized rats, we have shown that D-amphetamine as well as methylphenidate dosedependently increases the time that the prefrontal cortex (PFC) spends in the Up state (TUP) (Shen and Shi, 2021)
Confirming our previous finding (Shen and Shi, 2021), D-amphetamine increased TUP and decreased PSO
Summary
During slow wave sleep and general anesthesia, the membrane potential of cortical neurons alternates between two preferred levels known as the Up and Down states (Neske, 2016; Poulet and Crochet, 2019). Amphetamine Promotes Cortical Up State et al, 2011; Polack et al, 2013; Einstein et al, 2017) Their occurrence increases with increasing sleep pressure (Nir et al, 2011; Vyazovskiy et al, 2011). A transition from Up/Down oscillations to a persistent Up state occurs during the transition from sleep to wake or from general anesthesia to an arousal state (Steriade et al, 2001; Constantinople and Bruno, 2011). The awake EEG is dominated by low-amplitude, high-frequency activities associated with the Up state
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