Effects of arousal- and feeding-related neuropeptides on dopaminergic and GABAergic neurons in the ventral tegmental area of the rat.
Many neuropeptides regulate feeding and arousal; the ventral tegmental area (VTA) is likely to be one site where they act. We used whole-cell patch-clamp and single-unit extracellular recordings to examine the effects of such neuropeptides on the activity of VTA neurons. Substance P (SP; 300 nM) increased the firing rate of the majority of VTA dopaminergic and gamma-aminobutyric acid (GABA)ergic neurons, and induced oscillations in two dopaminergic cells. Corticotropin-releasing factor (CRF; 200 nM) excited the majority of VTA cells directly, whereas neuropeptide Y (NPY; 300 nM) directly inhibited a subset of dopaminergic and GABAergic cells. Consecutive application of several neuropeptides revealed that all the neurons were excited by at least one of the excitatory neuropeptides SP, CRF or/and orexins. Alpha-melanocyte-stimulating hormone had no effect on dopaminergic cells (at concentrations of 500 nM and 1 microM) and affected only a small proportion of GABAergic neurons. Ghrelin (500 nM), agouti-related peptide (1 microM); cocaine and amphetamine-related transcript (500 nM) and leptin (500 nM and 1 microM) did not modulate the firing rate and membrane potential of VTA neurons. Single-cell reverse transcription polymerase chain reaction analysis showed that all NPY receptors were present in VTA neurons, and all but one cell expressed NPY and/or at least one NPY receptor. CRF was expressed in 70% of dopaminergic VTA cells; the expression of CRF receptor 2 was more abundant than that of receptor 1. These findings suggest a link between the ability of neuropeptides to promote arousal and their action on VTA neurons.
Korotkova
T M
TM
Institute for Neurophysiology, Heinrich-Heine University, D-40001 Düsseldorf, Germany. tatiana.korotkova@uni-duesseldorf.de
Brown
R E
RE
Sergeeva
O A
OA
Ponomarenko
A A
AA
Haas
H L
HL
D000818:Animals; D001143:Arousal / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D005247:Feeding Behavior / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017557:Ventral Tegmental Area / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D009479:Neuropeptides; D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D004298:Dopamine