TY - JOUR
T1 - Enhancing excitability of dopamine neurons promotes motivational behaviour through increased action initiation
AU - Boekhoudt, Linde
AU - Wijbrans, Ellen C.
AU - Man, Jodie H. K.
AU - Luijendijk, Mieneke C. M.
AU - de Jong, Johannes W.
AU - van der Plasse, Geoffrey
AU - Vanderschuren, Louk J. M. J.
AU - Adan, Roger A. H.
PY - 2018
Y1 - 2018
N2 - Motivational deficits are a key symptom in multiple psychiatric disorders, including major depressive disorder, schizophrenia and addiction. A likely neural substrate for these motivational deficits is the brain dopamine (DA) system. In particular, DA signalling in the nucleus accumbens, which originates from DA neurons in the ventral tegmental area (VTA), has been identified as a crucial substrate for effort-related and activational aspects of motivation. Unravelling how VTA DA neuronal activity relates to motivational behaviours is required to understand how motivational deficits in psychiatry can be specifically targeted. In this study, we therefore used designer receptors exclusively activated by designer drugs (DREADD) in TH:Cre rats, in order to determine the effects of chemogenetic DA neuron activation on different aspects of motivational behaviour. We found that chemogenetic activation of DA neurons in the VTA, but not substantia nigra, significantly increased responding for sucrose under a progressive ratio schedule of reinforcement. More specifically, high effort exertion was characterized by increased initiations of reward-seeking actions. This effect was dependent on effort requirements and instrumental contingencies, but was not affected by sucrose pre-feeding. Together, these findings indicate that VTA DA neuronal activation drives motivational behaviour by facilitating action initiation. With this study, we show that enhancing excitability of VTA DA neurons is a viable strategy to improve motivational behaviour.
AB - Motivational deficits are a key symptom in multiple psychiatric disorders, including major depressive disorder, schizophrenia and addiction. A likely neural substrate for these motivational deficits is the brain dopamine (DA) system. In particular, DA signalling in the nucleus accumbens, which originates from DA neurons in the ventral tegmental area (VTA), has been identified as a crucial substrate for effort-related and activational aspects of motivation. Unravelling how VTA DA neuronal activity relates to motivational behaviours is required to understand how motivational deficits in psychiatry can be specifically targeted. In this study, we therefore used designer receptors exclusively activated by designer drugs (DREADD) in TH:Cre rats, in order to determine the effects of chemogenetic DA neuron activation on different aspects of motivational behaviour. We found that chemogenetic activation of DA neurons in the VTA, but not substantia nigra, significantly increased responding for sucrose under a progressive ratio schedule of reinforcement. More specifically, high effort exertion was characterized by increased initiations of reward-seeking actions. This effect was dependent on effort requirements and instrumental contingencies, but was not affected by sucrose pre-feeding. Together, these findings indicate that VTA DA neuronal activation drives motivational behaviour by facilitating action initiation. With this study, we show that enhancing excitability of VTA DA neurons is a viable strategy to improve motivational behaviour.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85034081656&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29153928
U2 - https://doi.org/10.1016/j.euroneuro.2017.11.005
DO - https://doi.org/10.1016/j.euroneuro.2017.11.005
M3 - Article
C2 - 29153928
SN - 0924-977X
VL - 28
SP - 171
EP - 184
JO - European neuropsychopharmacology
JF - European neuropsychopharmacology
IS - 1
ER -