ReviewGlutamate transmission in addiction
Section snippets
Glutamatergic pathways
Although glutamate is a ubiquitous neurotransmitter in brain, certain glutamatergic projections are thought to be critically impacted by addictive drugs. Notably, research focus has been brought to bear on glutamatergic afferents to the basal ganglia, in particular to the nucleus accumbens (Kalivas and O'Brien, 2008, Wolf, 1998). This includes inputs from the amygdala, hippocampus, medial thalamus and prefrontal cortex (Groenewegen et al., 1996). With the exception of the medial thalamus, all
Glutamate in the VTA in the development of addictive behaviors
The first indication that glutamate was involved in drug addiction emerged from the studies into the neurobiology of locomotor sensitization. The motor stimulant effects elicited by most addictive drugs generally augments with repeated drug administration, and this sensitized behavioral response can endure for months after the last repeated drug administration (Berridge and Robinson, 1998). While many investigators in the 1980s linked behavioral sensitization metaphorically to glutamatergic
Glutamate in the nucleus accumbens and the expression of addiction-related behaviors
A role for glutamate release into the nucleus accumbens in the expression of behavioral sensitization was first shown by blocking AMPA receptors in the nucleus accumbens (Pierce et al., 1996a). These authors also first brought focus to a potential preferential role of the core subcompartment of the nucleus accumbens in the expression of addiction-related behaviors by showing cocaine-induced release of glutamate in the core, but not the shell of animals expressing behavioral sensitization (
Glutamate as a pharmacotherapeutic target: focus on indirect regulation of synaptic glutamate release in the accumbens
The apparent role of glutamate in regulating both the development and expression of addictive behaviors in animal models identifies glutamate as a potential pharmacotherapeutic target. Primary in this consideration would seem the role of glutamate in the nucleus accumbens in mediating the expression of addictive behaviors as this may be related to the vulnerability to relapse to drug-taking that characterizes human addiction (Kalivas and Volkow, 2005). While it is possible to simply block AMPA
Summary of glutamate transmission in the induction and expression of addiction-related behaviors
Glutamate plays a crucial role in regulating both the development and expression of addictive behaviors, such as sensitization and drug-seeking. The development of addiction-related behaviors requires glutamate receptor stimulation in the VTA and is associated with enhanced glutamate release and transient LTP in dopamine cells. In contrast, the expression of sensitization and drug-seeking requires glutamate release into the core of the nucleus accumbens. The glutamate arises from both the
Acknowledgements
A portion of the research summarized in this review was supported by the National Institute of Drug Abuse (#DA015369, DA03906, DA12513, DA015851).
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