Methamphetamine acutely alters frontostriatal resting state functional connectivity in healthy young adults

Abstract

Chronic use of methamphetamine impairs frontostriatal structure and function, which may result in increased incentive-motivational responses to drug cues and decreased regulation of drug-seeking behavior. However, less is known regarding how the drug affects these circuits after acute administration. The current study examined the effects of a single dose of methamphetamine on resting state frontostriatal functional connectivity in healthy volunteers. Participants (n = 22, 12 female) completed two sessions in which they received methamphetamine (20 mg) and placebo before a resting state scan during functional magnetic resonance imaging. Participants also provided self-report measures of euphoria and stimulation at regular intervals. We conducted seed-based voxelwise functional connectivity analyses using three bilateral striatal seed regions: nucleus accumbens (NAcc), caudate, and putamen and compared connectivity following methamphetamine versus placebo administration.Additionally, we conducted correlational analyses to assess if drug-induced changes in functional connectivity were related to changes in subjective response.Methamphetamine increased NAcc functional connectivity with medial frontal regions (ie, orbitofrontal cortex, medial frontal gyrus, and superior frontal gyrus) and decreased NAcc functional connectivity with subgenual anterior cingulate cortex (ACC). Methamphetamine also increased functional connectivity between putamen and left inferior frontal gyrus (IFG), and individuals who displayed greater druginduced increase in connectivity reported less euphoria and stimulation. These findings provide important information regarding the effects of methamphetamine on brain function in nonaddicted individuals. Further studies will reveal whether such effects contribute to the abuse potential of the drug and whether they are related to the frontostriatal impairments observed after chronic methamphetamine use.

Anticipation of monetary reward in amygdala, insula, caudate are predictors of pleasure sensitivity to d-Amphetamine administration

“…Positive subjective responses to stimulants are also related to dopamine cell activity, levels of D2 receptors, and level of D2/D3 receptor binding (Abi-Dargham et al, 2003;Calipari et al, 2015;Drevets et al, 2001;Leyton et al, 2002;Martinez et al, 2003;Volkow et al, 2002). We recently reported that, in healthy volunteers, methamphetamine acutely increases resting state functional connectivity between the striatum and medial and lateral frontal regions, and that less drug-induced connectivity between the putamen and left inferior frontal gyrus is associated with greater drug-induced euphoria (Weafer, Van Hedger et al 2019). Chronic use of stimulants is associated with lower dopamine release, transporter availability and D2/D3 availability (Ashok et al, 2017;Letchworth et al, 2001).…”

Acute alcohol intake alters resting state functional connectivity of nucleus accumbens with pain-related corticolimbic structures

“…Thus, the noted alcohol-related reduction in NAc-mPFC rsFC suggests a potential mechanism by which alcohol may influence pain. The directionality of this effect was opposite of acute methamphetamine (Weafer et al, 2019), suggesting that drugs of abuse likely differ in their effects on corticolimbic rsFC.…”

Effects of Methamphetamine on Within- and Between-Network Connectivity in Healthy Adults

“…2005 ). That said, Weafer et al. (2020 ) examined relationships between subjective responses to MA and drug-induced changes in FC in a seed-based, frontally focused analysis and found that individuals who exhibited greater drug-induced increase in FC between left inferior frontal gyrus and putamen reported less euphoria and stimulation.…”

“…2016 ; Gorka et al. 2020 ; Weafer et al. 2020 ), perhaps because they targeted selected brain regions of a priori interest.…”