Morphine-induced activation of A10 dopamine neurons in the rat.
The effects of intravenous administration of morphine (MOR) on the spontaneous discharge rate of dopamine (DA) neurons in the ventral tegmental area (VTA or A10) and the substantia nigra pars compacta (SNC or A9) were compared. MOR (0.5-3.5 mg/kg) produced a marked increase in the spontaneous firing of both A10 and A9 DA neurons. Naloxone (NAL) reversed the MOR effects. Acute transection of the medial forebrain bundle (MFB) did not interfere with the observed MOR effects on either A10 or A9 DA neurons. However, following chronic lesions of the MFB (6 days), A9 DA neurons were no longer responsive to MOR whereas A10 DA cells were still activated by MOR. Neither radiofrequency lesions of the dorsal raphe nucleus (DRN) nor administration of the 5-HT2 antagonist ketanserin affected the stimulatory effect of MOR on either A10 or A9 DA cells. Thus, it is confirmed that the effects of MOR on A9 DA cells depend on striatonigral feedback pathways. In contrast, it appears that the MOR-induced activation of A10 DA cells does not depend on afferents from the forebrain or on projections from the DRN, suggesting a more direct action of MOR on A10 DA cells. Microiontophoretic application of MOR or enkephalin analogues significantly increased the spontaneous activity of both A9 and A10 DA cells. However, these effects were not reversed by either iontophoretic or intravenous NAL. On the other hand, both intravenously (0.5-1.5 mg/kg) and iontophoretically administered MOR markedly suppressed the electrical activity of non-DA cells found in the vicinity of A10 DA neurons, and this effect was completely reversed by NAL. It is proposed that the MOR-induced activation of A10 DA cells could be mediated indirectly by non-DA cells.
D000818:Animals; D004298:Dopamine / Q000502:physiology*; D008032:Limbic System / Q000187:drug effects*; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology; D009020:Morphine / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects*; D013681:Tegmentum Mesencephali / Q000187:drug effects*
D011957:Receptors, Opioid; D009020:Morphine; D004298:Dopamine