• Ingo Willuhn, Lauren M Burgeno, Peter A Groblewski, and Paul E M Phillips.
• 1] Department of Psychiatry & Behavioral Sciences, University of Washington, Seattle, Washington, USA. [2] Department of Pharmacology, University of Washington, Seattle, Washington, USA. [3].
• Nat. Neurosci. 2014 May 1;17(5):704-9.

AbstractDrug addiction is a neuropsychiatric disorder marked by escalating drug use. Dopamine neurotransmission in the ventromedial striatum (VMS) mediates acute reinforcing effects of abused drugs, but with protracted use the dorsolateral striatum is thought to assume control over drug seeking. We measured striatal dopamine release during a cocaine self-administration regimen that produced escalation of drug taking in rats. Surprisingly, we found that phasic dopamine decreased in both regions as the rate of cocaine intake increased, with the decrement in dopamine in the VMS significantly correlated with the rate of escalation. Administration of the dopamine precursor L-DOPA at a dose that replenished dopamine signaling in the VMS reversed escalation, thereby demonstrating a causal relationship between diminished dopamine transmission and excessive drug use. Together these data provide mechanistic and therapeutic insight into the excessive drug intake that emerges following protracted use.

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