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.
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 microM quinpirole was reduced by approximately 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.
Werkman
T R
TR
Institute for Neurobiology, University of Amsterdam, The Netherlands.
Kruse
C G
CG
Nievelstein
H
H
Long
S K
SK
Wadman
W J
WJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D016015:Logistic Models; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D009496:Neurotensin / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors; D013378:Substantia Nigra / Q000166:cytology*; D017557:Ventral Tegmental Area / Q000166:cytology*
D018491:Dopamine Agonists; D007093:Imidazoles; D010446:Peptide Fragments; D018028:Receptors, Neurotensin; C104418:SR 142948A; D019257:Quinpirole; D009496:Neurotensin; C054381:neurotensin (8-13); D000218:Adamantane; D004298:Dopamine