Decreasing Striatal 6-FDOPA Uptake with Increasing Duration of Cocaine Withdrawal

Abstract

It has been hypothesized that a decrease in dopaminergic presynaptic activity during abstinence or withdrawal is related to relapse in cocaine-dependent subjects (Dackis and Gold 1985;Markou and Koob 1991). This study measured striatal Cocaine is one of the most potent and reinforcing central nervous system stimulants (Withers et al. 1995). Cocaine's pharmacological effects are due to its binding of the dopamine transporter molecule, thereby increasing intrasynaptic dopamine concentration (Giros et al. 1996). Seventy-five percent of patients who withdraw from cocaine abuse relapse within a year (Paredes et al. 1991;Carroll et al. 1994 Gawin and Kleber (1986), Martin et al. (1989a), andSatel et al. (1991) found that there was a delayed cocaine craving with approximately 10 days of abstinence from cocaine. Gawin and Kleber (1986) have described a triphasic course during abstinence from cocaine for outpatients. The first phase is described as a crash phase with extreme dysphoria and hypersomnolence lasting 1 to 40 h. The second phase is described as the withdrawal period lasting up to 10 weeks. This phase is subdivided into two subphases. The early subphase is characterized initially by little cocaine craving, nearnormal affective functioning, and normal sleep/wake cycles, and it lasts several days. The middle and late subphase is characterized by high cocaine craving, dysphoria, anhedonia, and anxiety and sensitivity to conditioned cues. Martin et al. (1989a) found that there was distinct increase in cocaine craving between 1 and 2 weeks after last cocaine use in six patients who were evaluated over a 21-day period during an inpatient recovery. Satel et al. (1991) found that there was an initial decrease in Beck Depression score between days 1-9

Brain dopaminergic system changes in drug addiction: a review of positron emission tomography findings

“…In cocaine addiction, PET imaging with [ 18 F] dopa (6-[ 18 F] fluoro-L-dopa) shows a delayed decrease in DA terminal activity in the striatum of detoxified cocaine abusers compared with controls [34,35] . Also, a decrease in presynaptic DA activity during cocaine abstinence or withdrawal is associated with relapse [36,37] .…”

“…Uptake of L-dopa labeled with a positron-emitting radionuclide refl ects the synthesis rate of DA in the terminals, under the conditions of PET [32,33] . Studies with PET and radionuclidelabeled L-dopa and their main fi ndings are summarized in [34,35] . Also, a decrease in presynaptic DA activity during cocaine abstinence or withdrawal is associated with relapse [36,37] .…”

Positron Emission Tomography Molecular Imaging of Dopaminergic System in Drug Addiction

“…It has been showed that a decrease in dopaminergic presynaptic activity during abstinence or withdrawal is related to relapse in cocaine-dependent subjects (Dackis and Gold, 1985;Markou and Koob, 1991). PET imaging with [ 18 F] dopa has found in the detoxified cocaine abusers a delayed decrease in DA terminal activity in the striatum compared with controls (Bell et al, 1996;Wu et al, 1997).In the study of Heinz et al (2005), although no difference of striatal [ 18 F] dopa net influx, an index of DA synthesis capacity, was found between detoxified alcoholic patients and the control subjects, the results showed that a low DA synthesis capacity correlated with alcohol craving which was associated with a high relapse risk.…”

Correspondence

“…A recent article in Neuropsychopharmacology (Wu et al 1997) reports the first attempt to assess with positron emission tomography (PET) the effects of chronic cocaine use on the cerebral influx of 6-[ 18 F]fluoro-L-DOPA (FDOPA), a tracer for DOPA decarboxylase in catecholamine fibers of living human brain. Other PET studies have probed the occupancy of dopamine uptake sites or post-synaptic receptors in cocaine users (Volkow et al 1996(Volkow et al , 1997.…”

“…The magnitude of K i is then estimated from linear regression of this distribution volume as a function of the normalized and metabolite-corrected integral of FDOPA in arterial plasma (Martin et al 1989). Wu et al (1997) employ an ingenious method for defining contiguous regions in brain for statistical comparisons of K i between subject groups, and for comparing effects of acute and chronic withdrawal from cocaine. However, it is not revealed how regions of interest (Figure 2) or reference regions in brain were delineated, nor is it explained how the HPLC fractionation of tracers in arterial plasma was accomplished.…”