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Keywords:

  • CART;
  • CRF;
  • NPY;
  • reward;
  • substance P

Abstract

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 γ-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. α-Melanocyte-stimulating hormone had no effect on dopaminergic cells (at concentrations of 500 nm and 1 µm) and affected only a small proportion of GABAergic neurons. Ghrelin (500 nm), agouti-related peptide (1 µm); cocaine and amphetamine-related transcript (500 nm) and leptin (500 nm and 1 µm) 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.