Cw. Bradberry et al., Impact of self-administered cocaine and cocaine cues on extracellular dopamine in mesolimbic and sensorimotor striatum in rhesus monkeys, J NEUROSC, 20(10), 2000, pp. 3874-3883
Studies were conducted to determine the impact of self-administered cocaine
on extracellular striatal dopamine in four rhesus monkeys. The extent to w
hich external cue conditioning contributed to the effects of cocaine and wh
ether there is activation of striatal dopaminergic neurotransmission during
drug-seeking behavior was also examined. Microdialysis measurements were m
ade at 2 min intervals in sensorimotor (dorsolateral) and mesolimbic (centr
al and ventromedial) striatum. A fixed-ratio schedule of reinforcement was
used, with cocaine availability signaled by a visual cue. Studies examined
the effects of cocaine or cocaine cues against a drug-free baseline. Large
(fivefold to eightfold) increases in extracellular dopamine after a self-ad
ministered infusion of 0.5 mg/kg cocaine were quite rapid and matched the t
ime course of reported subjective effects in human laboratory studies. To d
etermine if conditioning to external cues contributed to the cocaine-induce
d increases, saline was substituted for cocaine in the infusion, leaving al
l other visual and auditory stimuli unchanged. No increase in extracellular
dopamine in either sensorimotor or mesolimbic striatal subdivisions was ob
served. Extracellular dopamine during extended periods of drug-seeking beha
vior triggered by a visual cue was determined in both central and ventromed
ial striatum. This procedure also did not result in any measurable changes
in extracellular dopamine. These studies demonstrate rapid and pronounced p
harmacological actions of self-administered cocaine. No apparent conditione
d component of those actions was associated with external environmental cue
s, suggesting that cues that trigger drug-seeking behavior in nonhuman prim
ates do not cause conditioned increases in mesolimbic striatal dopamine.