Dopamine increases in striatum do not elicit craving in cocaine abusers unless they are coupled with cocaine cues
Section snippets
Subjects
Twenty active cocaine-addicted subjects who responded to an advertisement were studied. Subjects fulfilled DSM-IV criteria for cocaine dependence and were active users for at least the prior 6 months (free-base or crack, at least “4 g” a week). Exclusion criteria included current or past psychiatric disease other than cocaine dependence; past or present history of neurological, cardiovascular or endocrinological disease; history of head trauma with loss of consciousness greater than 30 min; and
Concentration of MP in plasma
The plasma levels of MP did not differ between the two conditions of administration. These levels corresponded for the cocaine cue and the neutral video conditions respectively to 3 ± 1 and 4 ± 3 ng/ml at 30 min; to 7 ± 3 and 7 ± 4 ng/ml at 60 min; to 7 ± 2 and 8 ± 3 ng/ml at 90 min; and to 5 ± 2 and 6 ± 2 ng/ml at 120 min after its administration. The correlation between plasma MP concentration and the cardiovascular, behavioral and DA measures were not significant.
Effects of MP on the cardiovascular measures when exposed to the cocaine video versus the neutral video
The changes in cardiovascular measures (pre −
DA and craving
Here we show that MP significantly increased extracellular DA in striatum but that it induced craving only when administered with the cocaine cue video. Moreover the craving measures were only elevated after the subjects had been exposed to the cocaine cue video but not prior to it. Though prior studies in cocaine abusers had shown that cue-induced DA increases in striatum were associated with craving (Volkow et al., 2006, Wong et al., 2006), the current findings indicate that striatal DA
Conclusion
Here we show that slow increases in DA as achieved with oral MP were not associated with craving when there was no concomitant presentation of conditioned cues. This suggests that DA increases associated with conditioned cues reflect secondary responses to activation of pathway(s) that modulate DA cell firing and release (i.e., fronto-striatal and fronto-mesencephalic glutamatergic pathways). Moreover fast DA changes as triggered by phasic DA cell firing may underlie craving rather than the
Acknowledgments
We thank David Alexoff, Pauline Carter, Barbara Hubbard, Lisa Muench, Kith Pradhan, Colleen Shea, David Schlyer, Michael Schueller, Paul Vaska, Don Warner, Youwen Xu, Karen Apelskog and Linda Thomas for their contributions. Research supported by NIH’s Intramural Research Program (NIAAA), NIDA (DA06278-15), GCRC (MO1RR10710) and by DOE (DE-AC01-76CH00016) and for Dr. Childress (VA VISN 4 MIRECC and the DANA Foundation).
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