On the role of glutamate within the locus coeruleus during the development of opioid dependence and on the expression of withdrawal from dependence on opioids

Abstract The development of dependence with repeated use and the expression of withdrawal syndrome are characteristic features of all the opioids represented by morphine. Although many studies regarding several neurotransmitters and receptors have been conducted to define the mechanism involved in the development of dependence on opioids, the definitive evidence has still not been presented. Hyperactivity of noradrenergic neurons within the locus coeruleus has been proposed to play a critical role in the physiological and behavioral responses that comprise opioid withdrawal. Furthermore, much recent interest has been focused on the putative involvement of glutamate within the locus coeruleus, as one member of the excitatory amino acid neurotransmitter family, in the development of dependence on opioids, since several results obtained from a variety of molecular biological, electrophysiological, biochemical, and behavioral studies indicate that glutamate and its receptors participate in both the withdrawal-associated increase in neuronal activity of locus coeruleus and the expression of opioid withdrawal behaviors. Therefore the present review will evaluate a recent trend regarding the role of glutamate within the locus coeruleus during the development of opioid dependence and on the expression of withdrawal from dependence on opioids.