Acute morphine administration increases extracellular DA levels in the rat lateral septum by decreasing the GABAergic inhibitory tone in the ventral tegmental area.

We studied the effect of an acute systemic administration of morphine and of a local intra-ventral tegmental area (VTA) infusion of the same drug on extracellular levels of dopamine (DA) in the lateral septum (LS) by in vivo microdialysis in anesthetized rats. The extracellular levels of 5-hydroxytryptamine (5-HT) were also measured in all dialysate samples. The acute systemic administration of morphine dose-dependently increased extracellular levels of DA but not of 5-HT in the LS, in the absence or presence of fluoxetine. This morphine effect was antagonized by the previous administration of naloxone, a specific opioid antagonist. The local infusion of morphine in the VTA also induced a significant increase of the extracellular levels of DA in the LS, concomitantly with a decrease of gamma-aminobutyric acid (GABA) extracellular levels in the VTA itself. Intriguingly, the LS extracellular levels of DA returned to basal values before the VTA GABA extracellular levels recovered. Our results show for the first time that an acute administration of morphine increases DA extracellular levels in the LS. The results also suggest that DA cells in the VTA and innervating the LS are under an inhibitory GABAergic tone sensitive to morphine. Taken together, our neurochemical data and previous studies involving LS DA in stress-related behavior support the hypothesis that DA in the LS plays a significant role in addictive behavior. The participation of LS DA and 5-HT systems in stress-induced relapse to drug seeking should be studied further.