Amphetamine Promotes Cortical Up State in Part Via Dopamine Receptors

Authors

Guofang Shen, Department of Pharmaceutical and Administrative Sciences, Loma Linda University School of Pharmacy, Loma Linda, CA, United States.
Wei-Xing Shi, Department of Pharmaceutical and Administrative Sciences, Loma Linda University School of Pharmacy, Loma Linda, CA, United States.Follow

Document Type

Article

Publication Date

1-1-2021

Publication Title

Frontiers in pharmacology

ISSN

1663-9812

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 α 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.

Volume

12

First Page

728729

DOI

10.3389/fphar.2021.728729

PubMed ID

34489713

Recommended Citation

Shen, Guofang and Shi, Wei-Xing, "Amphetamine Promotes Cortical Up State in Part Via Dopamine Receptors" (2021). Loma Linda University Faculty Publications. 406.
https://scholarsrepository.llu.edu/fac_pubs/406