Dopamine D2 receptor availability in opiate-dependent subjects before and after naloxone-precipitated withdrawal.
Dopamine may play a role in opiate withdrawal and dependence. We measured dopamine D2 receptor availability in 11 opiate-dependent subjects using PFT and [11C]raclopride at baseline and during naloxone-precipitated withdrawal. Because [11C]raclopride is sensitive to endogenous dopamine, this strategy enabled us to test whether we could document in humans the DA reductions reported in animal models of opiate withdrawal. Results were compared with values from 11 controls, two of which also received naloxone. The ratio of the distribution volume in striatum to that in cerebellum (Bmax/Kd + 1) was used as model parameter for D2 receptor availability. Baseline measures for Bmax/Kd were lower in opiate-dependent subjects (2.44 +/- 0.4) than in controls (2.97 +/- 0.45 P < or = .009). Naloxone precipitated an intense withdrawal in the abusers but did not change the Bmax/Kd ratio. This study documents decreases in D2 receptors in opiate-dependent subjects but does not document significant changes in striatal DA concentration during acute withdrawal.
Wang
G J
GJ
Department of Medicine, Brookhaven National Laboratory, Upton, NY, USA.
Volkow
N D
ND
Fowler
J S
JS
Logan
J
J
Abumrad
N N
NN
Hitzemann
R J
RJ
Pappas
N S
NS
Pascani
K
K
D000328:Adult; D001479:Basal Ganglia / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D019966:Substance-Related Disorders / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D009294:Narcotics; D017448:Receptors, Dopamine D2; D009270:Naloxone