title: Changes in dopamine transporter binding in nucleus accumbens following chronic self-administration cocaine: heroin combinations.
abstract: Concurrent use of cocaine and heroin (speedball) has been shown to exert synergistic effects on dopamine neurotransmission in the nucleus accumbens (NAc), as observed by significant increases in extracellular dopamine levels and compensatory elevations in the maximal reuptake rate of dopamine. The present studies were undertaken to determine whether chronic self-administration of cocaine, heroin or a combination of cocaine:heroin led to compensatory changes in the abundance and/or affinity of high- and low-affinity DAT binding sites. Saturation binding of the cocaine analog [(125) I] 3β-(4-iodophenyl)tropan-2β-carboxylic acid methyl ester ([(125) I]RTI-55) in rat NAc membranes resulted in binding curves that were best fit to two-site binding models, allowing calculation of dissociation constant (Kd ) and binding density (Bmax ) values corresponding to high- and low-affinity DAT binding sites. Scatchard analysis of the saturation binding curves clearly demonstrate the presence of high- and low- affinity binding sites in the NAc, with low-affinity sites comprising 85 to 94% of the binding sites. DAT binding analyses revealed that self-administration of cocaine and a cocaine:heroin combination increased the affinity of the low-affinity site for the cocaine congener RTI-55 compared to saline. These results indicate that the alterations observed following chronic speedball self-administration are likely due to the cocaine component alone; thus further studies are necessary to elaborate upon the synergistic effect of cocaine:heroin combinations on the dopamine system in the NAc.
authors.affiliation: Graduate Program in Neuroscience, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157; Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina, 27157.
authors.forename: Lindsey P
authors.initials: LP
authors.lastname: Pattison
authors.forename: Scot
authors.initials: S
authors.lastname: McIntosh
authors.forename: Tammy
authors.initials: T
authors.lastname: Sexton
authors.forename: Steven R
authors.initials: SR
authors.lastname: Childers
authors.forename: Scott E
authors.initials: SE
authors.lastname: Hemby
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004338:Drug Combinations; D003932:Heroin / Q000008:administration & dosage*; D013287:Illicit Drugs; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D009294:Narcotics / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D019275:Radiopharmaceuticals; D011916:Rats, Inbred F344; D012646:Self Administration
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D004338:Drug Combinations; D013287:Illicit Drugs; D007457:Iodine Radioisotopes; D009294:Narcotics; D019275:Radiopharmaceuticals; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003932:Heroin; D003042:Cocaine
keywords: drug abuse; drug addiction; neuropharmacology; operant conditioning; polydrug; psychopharmacology; reinforcement; speedball