Relationship between incubated methamphetamine craving and frontal cortical expression of dopamine receptors

Globally, methamphetamine use disorder (MUD) poses a significant public health concern. Notably, re-exposure to methamphetamine-associated cues elicits a very intense craving that intensifies over the first 1-6 months into withdrawal, rendering abstinent individuals highly vulnerable to relapse. The neurobiological mechanisms driving this incubated craving are not known. Cue-elicited craving is associated with a hyper-activation of the frontal cortex in humans with MUD. Methamphetamine induces the release of dopamine within the frontal cortex which, after prolonged use, causes alterations in dopamine receptor expression that may underlie incubated craving for methamphetamine. Contrary to our hypothesis, we found that there was a lack of incubated craving-related changes in dopamine receptor expression in both prelimbic and infralimbic cortices, with only dopamine receptor 1 being downregulated in methamphetamine experienced males, but not sham males. This decrease in dopamine receptor 1 does not mediate the incubation of methamphetamine craving as it is methamphetamine-specific rather than a time dependent change.