title: Inhibitory effects of ventral tegmental area stimulation on the activity of prefrontal cortical neurons: evidence for the involvement of both dopaminergic and GABAergic components.
abstract: The medial prefrontal cortex of the rat receives dopamine and non-dopaminergic projections from the ventral tegmental area. Both electrical stimulation of the ventral tegmental area and local application of dopamine induce an inhibition of the spontaneous activity of most prefrontal cortical neurons, including efferent neurons. In the present study, the techniques of extracellular recording and microiontophoresis were used in anesthetized rats in order to determine whether these dopamine- and ventral tegmental area-induced inhibitory responses involve GABAergic components. Prefrontal cortex output neurons were identified by antidromic activation from subcortical structures. The inhibitory responses evoked by the local application of dopamine were blocked by the iontophoretic application of the D2 antagonist sulpiride, and the GABAA antagonist bicuculline in 89 and 57% of the cases, respectively. In addition, sulpiride and bicuculline abolished the inhibition induced by ventral tegmental area stimulation in 54 and 51% of the prefrontal cortical cells tested, respectively. The implication of a non-dopaminergic mesocortical system in the ventral tegmental area-induced inhibition was further analysed using rats pre-treated with alpha-methylparatyrosine to deplete dopamine stores. The proportion of prefrontal cortical cells inhibited by ventral tegmental area stimulation was markedly reduced (39%) in alpha-methylparatyrosine-treated rats, when compared to controls (86%). Remaining ventral tegmental area-induced inhibition was no longer affected by sulpiride, but in all cases blocked by the local microiontophoretic application of bicuculline. The present results suggest that: (1) the dopamine-induced inhibition of prefrontal cortex neurons could involve cortical GABAergic interneurones; (2) the non-dopaminergic mesocortical system exerts also an inhibitory influence on prefrontal cortical cells and appears to be GABAergic.
authors.affiliation: INSERM U114, Chaire de Neuropharmacologie, Collège de France, Paris.
authors.forename: S
authors.initials: S
authors.lastname: Pirot
authors.forename: R
authors.initials: R
authors.lastname: Godbout
authors.forename: J
authors.initials: J
authors.lastname: Mantz
authors.forename: J P
authors.initials: JP
authors.lastname: Tassin
authors.forename: J
authors.initials: J
authors.lastname: Glowinski
authors.forename: A M
authors.initials: AM
authors.lastname: Thierry
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005625:Frontal Lobe / Q000502:physiology*; D007478:Iontophoresis; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013469:Sulpiride / Q000494:pharmacology*; D013681:Tegmentum Mesencephali / Q000502:physiology*; D013787:Thalamic Nuclei / Q000187:drug effects / Q000502:physiology; D019805:alpha-Methyltyrosine; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D008781:Methyltyrosines; D005680:gamma-Aminobutyric Acid; D019805:alpha-Methyltyrosine; D013469:Sulpiride; D004298:Dopamine; D001640:Bicuculline