Activation of dopaminergic and cholinergic neurotransmission by tachykinin NK3 receptor stimulation: an in vivo microdialysis approach in guinea pig.
The regulation of dopaminergic and cholinergic function by neurokinin-3 (NK3) receptor activation was examined in vivo in urethane-anaesthetized guinea pigs with microdialysis probes. The local application of the NK3 tachykinin receptor agonist senktide in the region of dopamine cell bodies (pars compacta of the substantia nigra and ventral tegmental area) and in the area of cholinergic cell bodies (septal area) markedly enhanced the extracellular dopamine (DA) and acetylcholine (ACh) concentration throughout their respective target areas, i.e. striatum, nucleus accumbens, prefrontal cortex for dopaminergic systems and hippocampus for cholinergic neurons. The enhancing effect of senktide on neurotransmitter release was dose dependently blocked by the selective non-peptide NK3 receptor antagonist SR142801 (0.1-1 mg/kg, i.p.), whereas its inactive S-enantiomer SR142806 (0.3-1 mg/kg, i.p.) did not exert any antagonistic activity on the effect of intranigral or intraseptal application of senktide. These results demonstrate that NK3 receptors can modulate the activity of central DA and ACh systems.
Marco
N
N
Sanofi Recherche - Neuropsychiatry Department, Montpellier, France.
Thirion
A
A
Mons
G
G
Bougault
I
I
Le Fur
G
G
Soubrié
P
P
Steinberg
R
R
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D013378:Substantia Nigra; D009435:Synaptic Transmission; D013997:Time Factors; D017557:Ventral Tegmental Area
D010446:Peptide Fragments; D010880:Piperidines; D018042:Receptors, Neurokinin-3; C054724:senktide; D013373:Substance P; C091554:SR 142801; D000109:Acetylcholine; D004298:Dopamine