Synaptic plasticity in the mesolimbic dopamine system

• Published in: Philosophical transactions of the Royal Society of London. Series B. Biological sciences 2003-04, Vol.358 (1432), p.815-819
• Main Authors: Thomas, Mark J., Malenka, Robert C.
• Format: Article
• Language: English
• Subjects: Addiction; Animals; Behavioral neuroscience; Cocaine; Cocaine - pharmacology; Dopamine; Dopamine - physiology; Dopamine agents; Dopamine Uptake Inhibitors - pharmacology; Drugs Of Abuse; Limbic System - physiology; Long term depression; Long term potentiation; Long-Term Potentiation - physiology; Mesencephalon - physiology; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Neurons; Neurons - physiology; New Directions; Nucleus Accumbens; Nucleus Accumbens - physiology; Plasticity; Synapses; Synapses - physiology; Ventral Tegmental Area
• ISSN: 0962-8436; 1471-2970
• DOI: 10.1098/rstb.2002.1236

Long-term potentiation (LTP) and long-term depression (LTD) are thought to be critical mechanisms that contribute to the neural circuit modifications that mediate all forms of experience-dependent plasticity. It has, however, been difficult to demonstrate directly that experience causes long-lasting changes in synaptic strength and that these mediate changes in behaviour. To address these potential functional roles of LTP and LTD, we have taken advantage of the powerful in vivo effects of drugs of abuse that exert their behavioural effects in large part by acting in the nucleus accumbens (NAc) and ventral tegmental area (VTA); the two major components of the mesolimbic dopamine system. Our studies suggest that in vivo drugs of abuse such as cocaine cause long-lasting changes at excitatory synapses in the NAc and VTA owing to activation of the mechanisms that underlie LTP and LTD in these structures. Thus, administration of drugs of abuse provides a distinctive model for further investigating the mechanisms and functions of synaptic plasticity in brain regions that play important roles in the control of motivated behaviour, and one with considerable practical implications.