Regulation of somatodendritic dopamine release in the ventral tegmental area by opioids and GABA: an in vivo microdialysis study.
Microdialysis of the ventral tegmental area in conscious rats was used to evaluate the influence of opioids and GABA agonists on extracellular levels of GABA and somatodendritically released dopamine. The administration of morphine through the dialysis probe elicited significant, dose-dependent increases in the levels of extracellular dopamine and significantly reduced the extracellular concentration of GABA. In contrast, a dose-dependent decrease in somatodendritic extracellular dopamine was produced following the administration of the GABAB agonist baclofen. The increase in dopamine levels elicited by morphine (100 microM) was completely blocked by either baclofen (100 microM) coadministration or peripheral injection of naloxone (2 mg/kg, i.p.). Application of the GABAA agonist muscimol produced a significant increase in both extracellular levels of dopamine and locomotor activity. The present results, together with other electrophysiological, neurochemical, and behavioral data, support a hypothesis that stimulation of mu-opioid or GABAA receptors inhibits the activity of GABAergic afferents to dopamine neurons, thereby removing tonic inhibitory regulation, whereas stimulation of GABAB receptors directly inhibits dopamine neurons.
Klitenick
M A
MA
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman 99164-6520.
DeWitte
P
P
Kalivas
P W
PW
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001692:Biological Transport; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D003956:Dialysis / Q000379:methods; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007395:Interneurons / Q000502:physiology; D007700:Kinetics; D008297:Male; D008959:Models, Neurological; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011963:Receptors, GABA-A; D009118:Muscimol; D009270:Naloxone; D005680:gamma-Aminobutyric Acid; D009020:Morphine; D001418:Baclofen; D004298:Dopamine