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Biphasic changes in mesolimbic dopamine signal during cocaine self-administration
1Department of Psychiatry, Medical College of Wisconsin, Milwaukee 53226.
Neuroreport
|April 14, 1994
Summary
Cocaine self-administration (SA) causes a rapid decrease in extracellular dopamine (DA) signaling in rats, suggesting inhibited DA release is linked to reward. This effect is distinct from DA reuptake inhibition.
Area of Science:
- Neuroscience
- Neuropharmacology
- Behavioral Neuroscience
Background:
- The mesolimbic dopamine (DA) system is crucial for reward and addiction.
- Understanding the real-time neurochemical changes during drug self-administration (SA) is key to elucidating addiction mechanisms.
Purpose of the Study:
- To investigate the immediate effects of cocaine SA on extracellular dopamine levels in the nucleus accumbens.
- To differentiate the roles of DA release and reuptake inhibition in cocaine's rewarding effects.
Main Methods:
- High-speed chronoamperometry using Nafion-coated carbon fiber microelectrodes.
- Measurement of extracellular dopamine in rat nucleus accumbens during intravenous cocaine and procaine SA.
Main Results:
- Cocaine SA induced an immediate, transient decrease in extracellular DA signal, followed by a slow increase preceding lever presses.
- Procaine SA also caused a dose-dependent DA signal decrease but lacked the pre-response increase.
- The observed DA decrease suggests short-term inhibition of DA release, independent of DA reuptake inhibition.
Conclusions:
- Short-term inhibition of mesolimbic DA release is an immediate consequence of cocaine SA and may mediate its rewarding properties.
- Cocaine exhibits dual actions on mesolimbic DA: inhibiting release and blocking reuptake, potentially contributing to its psychogenic and addictive effects.