Subsecond dopamine release in the ventral and dorsolateral striatum during the development of compulsive drug taking

• Applicant: Ingo Willuhn, Ph.D.
• Subject Area: Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
• Term: from 2010 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 161582268

The development of drug addiction is hallmarked by the transition from recreational to compulsive and escalated drug use. Drug taking is regulated by dopamine neurotransmission in the ventral striatum. However, during the transition from recreational to compulsive drug use the control of drug taking is thought to shift from the ventral to the dorsolateral striatum. We recently characterized phasic dopamine release in the ventral striatum during cocaine self-administration in rats with modest drug experience, analogous to recreational drug use in humans. Here, we propose to extend this work by using fast-scan cyclic voltammetry (FSCV) to measure subsecond dopamine signaling simultaneously in the ventral and dorsolateral striatum in rats accumulating excessive drug experience. For this purpose, we have developed and characterized a microelectrode for FSCV that can be implanted chronically for longitudinal detection of dopamine dynamics. To specifically study the transition from recreational to compulsive drug abuse, rats implanted with these electrodes and catheters for intravenous cocaine self-administration will be tested in a model of addiction that implements extended access to drug. This model has been shown to reliably produce a gradual escalation of drug intake and other traits that model criteria for drug addiction in humans. Thus, we will measure neurochemical changes related to drug taking before, during and after the development of compulsive drug intake. Phasic dopamine signaling in rats that show escalated cocaine intake is expected to undergo dynamic changes that reflect the development of compulsive drug abuse, including an anatomical shift from the ventral to the dorsolateral striatum.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Paul E. M. Phillips, Ph.D.