Effects of cocaine self-administration history under limited and extended access conditions on in vivo striatal dopamine neurochemistry and acoustic startle in rhesus monkeys.
BACKGROUND
The transition from infrequent and controlled cocaine use to dependence may involve enduring changes in neurobiology as a consequence of persistent drug use.


OBJECTIVE
The present study utilized an intravenous drug self-administration protocol of increasing cocaine access to evaluate potential changes in dopamine function in vivo, including changes in sensitivity to psychostimulants.


METHODS
Drug-naïve rhesus monkeys were provided limited access (1 h) to cocaine self-administration for 60 days followed by 60 days under an extended access condition (4 h). Basal levels of striatal extracellular dopamine and its metabolites, as well as the effectiveness of cocaine and amphetamine to elevate dopamine, were determined with in vivo microdialysis before the initiation of cocaine self-administration and during limited and extended access. The effect of cocaine and amphetamine on the acoustic startle response was also examined to assess complementary behavioral changes as a function of drug history.


RESULTS
Extended access to cocaine self-administration lead to increased daily intake compared to limited access conditions but did not result in escalated intake over time. However, cocaine- and amphetamine-induced increases in striatal dopamine were diminished as a function of cocaine self-administration history. Surprisingly, there was no effect of drug-taking history on sensitivity to psychostimulant-induced enhancement of startle amplitude.


CONCLUSIONS
The present experiments provide evidence of a hypofunctional dopamine system that is not associated with an escalation in drug intake or reflected in measures of acoustic startle.
Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA.
Porche'
P
Kirkland Henry
Michael
M
Davis
Leonard L
LL
Howell
D000161:Acoustic Stimulation / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055664:Electrochemical Techniques / Q000379:methods; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D008253:Macaca mulatta / Q000502:physiology*; D008297:Male; D017551:Microdialysis / Q000379:methods; D010636:Phenols / Q000378:metabolism; D011571:Psychoacoustics; D013216:Reflex, Startle / Q000187:drug effects*; D012055:Reinforcement Schedule; D012646:Self Administration / Q000379:methods; D013343:Styrenes / Q000378:metabolism; D013997:Time Factors
C102377:1-(4'-hydroxyphenyl)-1-(aminomethyl)ethene; D018765:Dopamine Uptake Inhibitors; D010636:Phenols; D013343:Styrenes; D003042:Cocaine; D004298:Dopamine; D006719:Homovanillic Acid