David Lovinger - Dopamine, Dope and Sleep

ViDA 2021 - Wed June 23rd 2021
David Lovinger
National Institute on Alcohol Abuse and Alcoholism
Dopamine, Dope and Sleep
Most psychoactive drugs alter sleep and long-term use and abuse of drugs can produce sleep disruption. Acute use of cannabis drugs generally promotes sleep, but long-term, heavy cannabis drug users experience sleep disruption. Indeed, sleep problems are often cited as a reason for relapse to cannabis use. The major psychoactive ingredient of cannabis drugs, delta-9-tetrahydrocannabinol (THC) is likely responsible for these effects. Given the role of dopamine (DA) in the neural effects of THC and other drugs of abuse, along with a growing literature implicating DA in the neural mechanisms of sleep, we have examined THC effects on sleep in mice using polysomnography and on striatal DA release using fast-scan cyclic voltammetry (FSCV). A chronic THC exposure regimen that produces tolerance to the drug alters sleep in a sex-dependent manner. Initial doses of THC enhanced non-rapid eye movement (NREM) sleep in both males and females. Following chronic exposure, both males and females showed tolerance to the sleep-inducing THC effects. Male mice exhibited reduced NREM sleep following this exposure, while female mice showed no such change but exhibited increased REM sleep. Examination of DA release in slices from dorsomedial and dorsolateral striatum (DMS and DLS) and nucleus accumbens (NAc), revealed region, sex and exposure-time-dependent THC effects. The largest chronic THC-induced changes were in DMS where males showed increased DA release after acute exposure on the 6th day after chronic exposure. In contrast, females showed decreased DA release in DMS after acute and on day 6 after chronic THC exposure, with similar effects in female DLS and NAc. We are currently exploring drug-induced DA changes in the different striatal subregions using dLight and in vivo fiber photometry. It will be interesting to examine how THC alters DA levels in vivo and how DA may contribute to the sex-dependent drug-induced sleep alterations.