Next, the role of glutamate in specific brain sites such as the ventral tegmental area VTA and nucleus accumbens NAcc , which are associated with the rewarding effects of drugs of abuse will be discussed. Although both natural and drug rewards activate similar systems in the brain, the stimulation of reward systems by drug rewards is often much more powerful than that produced by natural rewards Wise, ; Koob, a ; Berridge and Robinson, ; Kelley and Berridge, ; Dileone et al. Over the last two decades, there has been an increasing focus on the role of the excitatory neurotransmitter glutamate in drug addiction.
Fixed-ratio schedules, in which the animal has to press a lever or poke its nose into a particular hole a fixed number of times to obtain the drug, are generally used to measure the reinforcing effects of a drug. The EAATs are located on glutamate terminals and presynaptic glial cells and play an important role in glutamate homeostasis O'Shea, ; Kalivas,
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Drug self-administration is the most robust and reliable model to measure the rewarding effects of drugs of abuse O'Connor et al. Over the last two decades, there has been an increasing focus on the role of the excitatory neurotransmitter glutamate in drug addiction.
Finally, heroin, which mainly binds to mu opioid receptors, alters glutamate transmission via several different mechanisms.
However, this review will restrict its focus on the role of glutamate in drug reward. Cocaine blocks DAT and increases dopamine levels, which mediates the rewarding effects of cocaine. This alcohol-induced increase in glutamate release is possibly due to inhibition of GABAergic interneurons that in turn inhibit presynaptic glutamate terminals.
In this review, pharmacological and genetic evidence supporting the role of glutamate in mediating the rewarding effects of the above described drugs of abuse will be discussed.
Drugs of abuse and alteration of glutamate transmission Drugs of abuse alter glutamate transmission via different mechanisms. In fact, drug-induced plasticity in glutamatergic transmission is critically involved in the development of drug addiction Kalivas, , ; van Huijstee and Mansvelder, Glutamate can also be transported back into the extrasynaptic space via the cystine-glutamate antiporter located on glial cells Lewerenz et al.