Neurotensin attenuates the quinpirole-induced inhibition of the firing rate of dopamine neurons in the rat substantia nigra pars compacta and the ventral tegmental area |
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| Affiliation: | 1. Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut Medical Center, Beirut, Lebanon;2. Department of Psychiatry, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon;1. King''s College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychology, London, UK;2. CASCAID, South London & Maudsley NHS Foundation Trust, London, UK;3. London South Bank University, London, UK;4. King''s College and NPF Centre of Excellence, Kings College Hospital NHS Foundation Trust, London, UK;5. King''s College Hospital NHS Foundation Trust, London, UK;6. Department of Neurology, Technical University Dresden, Fetscherstraße 74, Dresden, Germany;1. “Behavior and Basal Ganglia” Research Unit (EA 4712), University of Rennes 1, Rennes, France;2. Department of Neurology, Rennes University Hospital, Rennes, France;3. Department of Psychiatry, Rennes University Hospital, Rennes, France;4. Department of Neurophysiology, Rennes University Hospital, Rennes, France |
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| Abstract: | In the present study we describe the excitatory effects of the bioactive peptide neurotensin on the electrical activity of dopamine neurons (simultaneously recorded) in the substantia nigra pars compacta and the ventral tegmental area. The neurotensin fragment (8–13) induced comparable increases in firing rate of the substantia nigra and ventral tegmental area dopamine neurons (EC50 values 30 and 45 nM, respectively). The neurotensin receptor antagonist SR142948A antagonized the excitatory effects of neurotensin fragment (8–13) (pA2 values 8.4 and 8.2, respectively). Furthermore, it was found that a low concentration of neurotensin fragment (8–13) (1 nM) attenuated the inhibition of the firing rate by the selective dopamine D2 receptor agonist quinpirole in both neuron types (e.g., the effect of 0.01 μM quinpirole was reduced by ≈60% in the presence of 1 nM neurotensin fragment [8–13]). Antagonism of this neurotensin fragment (8–13) effect by SR142948A confirms that neurotensin receptors can reduce the effect of dopamine D2 receptors at the single-cell level.These results are discussed in the light of possible roles for neurotensin in neurological disorders such as Parkinson's disease and schizophrenia. |
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