One hour, but not six hours, of daily access to self-administered cocaine results in elevated levels of the dopamine transporter.
We have previously shown that brief (1 h) and extended (6 h) daily access to IV cocaine self-administration produce different behavioral and neural consequences following 2 weeks of drug withdrawal. Brief daily access produced stable consumption of the drug and, after withdrawal, a sensitized locomotor response and an enhanced c-Fos labeling to a single cocaine challenge. In contrast, extended daily cocaine self-administration produced escalation of drug consumption over trials but no enhanced behavioral or neurochemical response after withdrawal. Cocaine affects dopaminergic (DA) function by binding to the presynaptic transporter and thereby preventing reuptake of the neurotransmitter-an action thought to be responsible for the drug's reinforcing properties. In an extension of our previous work, the current study, using receptor autoradiography, compared binding (by [3H]WIN35428) of the dopamine transporter (DAT) in animals having experienced either brief or extended daily access to cocaine over 8 days, followed by 14 days of withdrawal. DAT densities were found to increase in the nucleus accumbens core (N.Acc Core) and the dorsal striatum (but not in the N.Acc shell, medial prefrontal cortex (mPFC), or ventral tegmental area (VTA)) of the 1-h, but not 6-h, subjects. In other words, elevations in DAT density were not associated with the 6-h access group, the group that models patterns of drug-use in human addicts, and therefore are likely to be independent of the neuroadaptations that occur in the "addictive" process. Such conclusions are also consistent with brain-imaging studies of human cocaine addicts. Additional research will be needed to identify the specific neural changes relevant to addiction.
Ben-Shahar
Osnat
O
Behavioral Pharmacology Laboratory, Department of Psychology, University of California, Santa Barbara, 93106-9660, USA. shahar@psych.ucsb.edu
Moscarello
Justin M
JM
Ettenberg
Aaron
A
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003216:Conditioning, Operant / Q000187:drug effects; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D014316:Tritium; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine