The link between dopamine function and apathy in cannabis users: an [F-18]-DOPA PET imaging study

TY - JOUR

T1 - The link between dopamine function and apathy in cannabis users

T2 - an [F-18]-DOPA PET imaging study

AU - Bloomfield, Michael A. P.

AU - Morgan, Celia J. A.

AU - Kapur, Shitij

AU - Curran, H. Valerie

AU - Howes, Oliver D.

PY - 2014/6

Y1 - 2014/6

N2 - Rationale Cannabis is the most widely used illicit drug in the world, and regular use has been associated with reduced motivation, i.e. apathy. Regular long-term cannabis use has been associated with reduced dopamine synthesis capacity. The mesolimbic dopaminergic system mediates the processing of incentive stimuli by modifying their motivational value, which in turn is modulated by endocannabinoid signalling. Thus, it has been proposed that dopaminergic dysfunction underlies the apathy associated with chronic cannabis use. Objectives The aim of this study was to examine the relationship between dopaminergic function and subjective apathy in cannabis users. Methods We measured dopamine synthesis capacity (indexed as the influx rate constant K (i) (cer) ) via 3,4-dihydroxy-6-[F-18]-fluoro-l-phenylalanine positron emission tomography and subjective apathy using the self-rated Apathy Evaluation Scale (AES-S) in 14 regular cannabis users. Results All subjects scored in excess of 34 points on the AES-S (median [interquartile range] 59.5 [7.5]), indicative of significant apathy based on normative data. K (i) (cer) was inversely correlated to AES-S score in the whole striatum and its associative functional subdivision (Spearman's rho = -0.64, p = 0.015 [whole striatum]; rho = -0.69, p = 0.006 [associative]) but not in the limbic or sensorimotor striatal subdivisions. There were no significant relationships between AES-S and current cannabis consumption (rho = 0.28, p = 0.34) or age of first cannabis use (rho = 0.25, p = 0.40). Conclusions These findings indicate that the reduction in striatal dopamine synthesis capacity associated with chronic cannabis use may underlie reduced reward sensitivity and amotivation associated with chronic cannabis use.

AB - Rationale Cannabis is the most widely used illicit drug in the world, and regular use has been associated with reduced motivation, i.e. apathy. Regular long-term cannabis use has been associated with reduced dopamine synthesis capacity. The mesolimbic dopaminergic system mediates the processing of incentive stimuli by modifying their motivational value, which in turn is modulated by endocannabinoid signalling. Thus, it has been proposed that dopaminergic dysfunction underlies the apathy associated with chronic cannabis use. Objectives The aim of this study was to examine the relationship between dopaminergic function and subjective apathy in cannabis users. Methods We measured dopamine synthesis capacity (indexed as the influx rate constant K (i) (cer) ) via 3,4-dihydroxy-6-[F-18]-fluoro-l-phenylalanine positron emission tomography and subjective apathy using the self-rated Apathy Evaluation Scale (AES-S) in 14 regular cannabis users. Results All subjects scored in excess of 34 points on the AES-S (median [interquartile range] 59.5 [7.5]), indicative of significant apathy based on normative data. K (i) (cer) was inversely correlated to AES-S score in the whole striatum and its associative functional subdivision (Spearman's rho = -0.64, p = 0.015 [whole striatum]; rho = -0.69, p = 0.006 [associative]) but not in the limbic or sensorimotor striatal subdivisions. There were no significant relationships between AES-S and current cannabis consumption (rho = 0.28, p = 0.34) or age of first cannabis use (rho = 0.25, p = 0.40). Conclusions These findings indicate that the reduction in striatal dopamine synthesis capacity associated with chronic cannabis use may underlie reduced reward sensitivity and amotivation associated with chronic cannabis use.

KW - Apathy

KW - Cannabis

KW - Drugs

KW - Dopamine

KW - Imaging

KW - Motivation

KW - PET

KW - POSITRON-EMISSION-TOMOGRAPHY

KW - CHRONIC MARIJUANA USERS

KW - PARKINSONS-DISEASE

KW - RAT-BRAIN

KW - DELTA(9)-TETRAHYDROCANNABINOL ACTS

KW - SYNAPTIC-TRANSMISSION

KW - HIPPOCAMPAL-NEURONS

KW - SIGNAL-TRANSDUCTION

KW - RECEPTOR-BINDING

KW - YOUNG ADULTHOOD

U2 - 10.1007/s00213-014-3523-4

DO - 10.1007/s00213-014-3523-4

M3 - Article

SN - 0033-3158

VL - 231

SP - 2251

EP - 2259

JO - Psychopharmacology

JF - Psychopharmacology

IS - 11

ER -