Proton Pump Inhibitor “Lansoprazole” Inhibits Locus Coeruleus’s Neuronal Activity and Increases Rapid Eye Movement Sleep

Abstract

Alteration of the bodily CO2 concentration and proton pump activity affects the sleep architecture. The brainstem locus coeruleus (LC) area plays an essential role in rapid eye movement (REM) sleep generation and chemoregulation. Previously, we reported that lansoprazole injections (intraperitoneal) increased REM sleep in the rats. However, it is not known if proton pumps in the LC influence REM sleep. Here, we studied the effects of lansoprazole in the LC on the neuronal activity and REM sleep expression. Male Wistar rats (250–300 g) were surgically prepared for sleep recording and drug microinjections into the LC. We determined the localization of proton pumps and expression levels of cFOS in the LC neurons immunohistochemically. Sleep–wake was recorded before and after the microinjections of drugs/vehicles. Our results demonstrate (i) the presence of proton pumps in the LC neurons, (ii) that the microinjection of lansoprazole into the LC reduced the number of cFOS+ve–TH+ve double-labeled neurons in the LC by 52.6% (p < 0.001) compared to the vehicle and (iii) that low and high doses of lansoprazole significantly increased REM sleep by 32% (p < 0.001) and 60% (p < 0.001), respectively, compared to the vehicle. Our results suggest that the proton pumps modulate the LC’s noradrenergic (NE-ergic) neuronal activity and REM sleep. The increased amount of REM sleep can be attributed to the inhibition of the LC NE-ergic activity. Further, the REM sleep amount increased after the lansoprazole microinjections into the LC with a significant increase in the REM sleep episode numbers. Overall, our results suggest that proton pumps in the LC may be involved in REM sleep generation.

Depression and Catatonia Associated With Lansoprazole in an Adolescent With Phelan-McDermid Syndrome

“…Depression, anxiety, delirium, and memory deficits have been observed after few days of PPI treatment, 1,12 whereas long-term use may be associated with increased risk of dementia 13 . Direct inhibition of noradrenergic neurons in the locus coeruleus by PPIs 14 may trigger depressive episodes by reducing rapid eye movement sleep latency and increasing rapid eye movement sleep duration 15,16 . Decreased serotoninergic tone may also contribute, 17 but evidence is less clear 18 .…”