Decomposing risky decision-making in methamphetamine use disorder: Behavioral updating and D2 dopamine receptors

Zoe Guttman; Mark Mandelkern; Dara G Ghahremani; Milky Kohno; Andy C Dean; Edythe D London

doi:10.1016/j.drugalcdep.2023.109860

Decomposing risky decision-making in methamphetamine use disorder: Behavioral updating and D2 dopamine receptors

Drug Alcohol Depend. 2023 May 1:246:109860. doi: 10.1016/j.drugalcdep.2023.109860. Epub 2023 Mar 29.

Authors

Zoe Guttman¹, Mark Mandelkern², Dara G Ghahremani¹, Milky Kohno³, Andy C Dean¹, Edythe D London⁴

Affiliations

¹ Department of Psychiatry and Biobehavioral Sciences and Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90024, USA.
² Veterans Administration of Greater Los Angeles Health System, Los Angeles, CA 90073, USA; Department of Physics, University of California at Irvine, Irvine, CA 92697, USA.
³ Department of Psychiatry, Oregon Health & Science University, Oregon Health Sciences University, Portland, OR 97239, USA.
⁴ Department of Psychiatry and Biobehavioral Sciences and Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90024, USA; Veterans Administration of Greater Los Angeles Health System, Los Angeles, CA 90073, USA; Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90024, USA; Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90024, USA. Electronic address: elondon@mednet.ucla.edu.

Abstract

Background: Escalating misuse of amphetamine-type stimulants, mainly methamphetamine, has led to a staggering rise in associated overdose deaths and a pressing need to understand the basis of methamphetamine use disorder (MUD). MUD is characterized by disadvantageous decision-making, and people with MUD perform below controls on the Balloon Analogue Risk Task (BART), a laboratory test of decision-making under uncertainty. The BART presents a series of choices with progressively higher stakes-greater risk of loss and greater potential monetary reward. This research aimed to clarify whether impaired behavioral updating contributes to maladaptive performance on the BART.

Methods: Two groups (28 drug-abstinent participants with MUD and 16 healthy control participants) were compared on BART performance. Using a computational model, we deconstructed behavior into risk-taking and behavioral updating. A subset of participants (22 MUD, 15 healthy control) underwent [¹⁸F]fallypride positron emission tomography scans to measure dopamine D2-type receptor availability (BPND) in the striatum (caudate and accumbens nuclei and putamen) and the globus pallidus.

Results: Participants with MUD exhibited slower behavioral updating than the healthy controls (p = 0.0004, d=1.77). BPND in all four bilateral volumes of interest were higher in the healthy control group (ps < 0.005, ds < 2.16), and updating rate correlated positively with BPND in the caudate nucleus (p = 0.002), putamen (p = 0.002), and globus pallidus (p = 0.03).

Conclusions: The findings indicate that behavioral updating contributes to maladaptive decision-making in MUD and suggest that dysregulation of D2-type receptor signaling in the striatum and globus pallidus contributes to this behavioral deficit.

Keywords: Computational psychiatry; Decision-making; Methamphetamine use disorder; Risk; Uncertainty.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural

MeSH terms

Amphetamine-Related Disorders*
Caudate Nucleus
Central Nervous System Stimulants* / adverse effects
Corpus Striatum / metabolism
Humans
Methamphetamine* / adverse effects
Positron-Emission Tomography / methods
Receptors, Dopamine D3 / metabolism

Substances

Methamphetamine
Central Nervous System Stimulants
Receptors, Dopamine D3

Abstract

Publication types

MeSH terms

Substances

Grants and funding