Effects of arousal‐ and feeding‐related neuropeptides on dopaminergic and GABAergic neurons in the ventral tegmental area of the rat

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.