Higher Levels of CSF Homovanillic Acid in Recently Abstinent Cocaine-Dependent Patients

Roy, Alec; Berman, J; Williams, R. F.; Kuhn, Cynthia M.; Gonzalez, Bienvenido

doi:10.1176/appi.ajp.159.6.1053

Cited by 9 publications

(3 citation statements)

References 8 publications

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“…Three previous studies found a correlation between cocaine craving and concentrations of the dopamine metabolite homovanillic acid (HVA) in either plasma or cerebrospinal fluid of cocaine abusers (Berger et al, 1996;Knoblich et al, 1992;Martin et al, 1989). A fourth study found higher levels of CSF HVA in recently abstinent cocaine-dependant patients as compared to controls, but no correlation between HVA levels and duration of abstinence (Roy et al, 2002). Administration of haloperidol, a dopamine receptor antagonist, reduced cue-induced cocaine craving in abstinent cocaine abusers in one study (Berger et al, 1996), but had a limited effect on subjective effects of cocaine in another (Sherer et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Increased Occupancy of Dopamine Receptors in Human Striatum during Cue-Elicited Cocaine Craving

Wong

Kuwabara

Schretlen

et al. 2006

Neuropsychopharmacol

277

214

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In all, 19 research subjects, with current histories of frequent cocaine use, were exposed to cocaine-related cues to elicit drug craving. We measured the change of occupancy of dopamine at D2-like receptors with positron emission tomography (PET) and inferred a change of intrasynaptic dopamine (endogenous dopamine release), based on the displacement of radiotracer [11 C]raclopride. Receptor occupancy by dopamine increased significantly in putamen of participants who reported cue-elicited craving compared to those who did not. Further, the intensity of craving was positively correlated with the increase in dopamine receptor occupancy in the putamen. These results provide direct evidence that occupancy of dopamine receptors in human dorsal striatum increased in proportion to subjective craving, presumably because of increased release of intrasynaptic dopamine.

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Section: Introductionmentioning

confidence: 99%

Increased Occupancy of Dopamine Receptors in Human Striatum during Cue-Elicited Cocaine Craving

Wong

Kuwabara

Schretlen

et al. 2006

Neuropsychopharmacol

277

214

View full text Add to dashboard Cite

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“…Recently, Alebouyeh et al (1) demonstrated the expression of human OAT1 and OAT3 in the ependymal epithelium of the choroid plexus facilitating the efflux of neurotransmitter metabolites, especially of VMA from the brain into the cerebrospinal fluid. OAT3 was also noted to be expressed in the blood-brain barrier, where it may be responsible for the elim- (38). This high K m value detected for rOAT3 leaves the question open regarding whether OAT3 contributes to HVA excretion from the brain under physiological conditions in vivo.…”

Section: Discussionmentioning

confidence: 99%

Murine renal organic anion transporters mOAT1 and mOAT3 facilitate the transport of neuroactive tryptophan metabolites

Bahn¹,

Ljubojević²,

Lorenz³

et al. 2005

American Journal of Physiology-Cell Physiology

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Tryptophan metabolites such as kynurenate (KYNA), xanthurenate (XA), and quinolinate are considered to have an important impact on many physiological processes, especially brain function. Many of these metabolites are secreted with the urine. Because organic anion transporters (OATs) facilitate the renal secretion of weak organic acids, we investigated whether the secretion of bioactive tryptophan metabolites is mediated by OAT1 and OAT3, two prominent members of the OAT family. Immunohistochemical analyses of the mouse kidneys revealed the expression of OAT1 to be restricted to the proximal convoluted tubule (representing S1 and S2 segments), whereas OAT3 was detected in almost all parts of the nephron, including macula densa cells. In the mouse brain, OAT1 was found to be expressed in neurons of the cortex cerebri and hippocampus as well as in the ependymal cell layer of the choroid plexus. Six tryptophan metabolites, including the bioactive substances KYNA, XA, and the serotonin metabolite 5-hydroxyindol acetate inhibited [(3)H]p-aminohippurate (PAH) or 6-carboxyfluorescein (6-CF) uptake by 50-85%, demonstrating that these compounds interact with OAT1 as well as with OAT3. Half-maximal inhibition of mOAT1 occurred at 34 muM KYNA and 15 muM XA, and it occurred at 8 muM KYNA and 11.5 muM XA for mOAT3. Quinolinate showed a slight but significant inhibition of [(3)H]PAH uptake by mOAT1 and no alteration of 6-CF uptake by mOAT3. [(14)C]-Glutarate (GA) uptake was examined for both transporters and demonstrated differences in the transport rate for this substrate by a factor of 4. Trans-stimulation experiments with GA revealed that KYNA and XA are substrates for mOAT1. Our results support the idea that OAT1 and OAT3 are involved in the secretion of bioactive tryptophan metabolites from the body. Consequently, they are crucial for the regulation of central nervous system tryptophan metabolite concentration.

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“…Although some studies have failed to find chronic cocaine-induced neurochemical changes (Kleven et al 1988;Yeh and De Souza 1991;, several preclinical studies have shown that chronic cocaine administration decreases D 1 receptor binding sites ), dopamine transporters (Sharpe et al 1991), dopamine uptake in the frontal cortex (Masserano et al 1994), and concentrations of dopamine and its metabolites, both peripherally ) and in the brain Karoum et al 1990Karoum et al , 1994. In humans, reduced dopamine levels in the frontal cortex, and both increases and decreases in number of dopamine transporters have been reported in post mortem studies of chronic cocaine abusers (Hitri et al 1994;Little et al 1996), and a decrease in dopamine terminal activity in the striatum (Wu et al 1997), higher levels of dopamine metabolites (Roy et al 2002), and changes in dopamine receptor binding (Volkow et al 1990) have been observed in vivo in abstinent cocaine abusers.…”

Section: Introductionmentioning

confidence: 99%

Transdermal selegiline and intravenous cocaine: safety and interactions

et al. 2003

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Higher Levels of CSF Homovanillic Acid in Recently Abstinent Cocaine-Dependent Patients

Abstract: Recently abstinent cocaine-dependent patients may show dysregulation of the central dopaminergic system.

Cited by 9 publications

References 8 publications

Increased Occupancy of Dopamine Receptors in Human Striatum during Cue-Elicited Cocaine Craving

Increased Occupancy of Dopamine Receptors in Human Striatum during Cue-Elicited Cocaine Craving

Murine renal organic anion transporters mOAT1 and mOAT3 facilitate the transport of neuroactive tryptophan metabolites

Transdermal selegiline and intravenous cocaine: safety and interactions

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