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 pe ptide neurotensin on the electrical activity of dopamine neurons (simultane ously recorded) in the substantia nigra pars compacta and the ventral tegme ntal area The neurotensin fragment (8-13) induced comparable increases in f iring rate of the substantia nigra and Ventral tegmental area dopamine neur ons (EC50 values 30 and 45 nM, respectively). The neurotensin receptor anta gonist SR142948A antagonized the excitatory effects of neurotensin fragment (8-13) (pA(2) 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 D-2 receptor ag onist quinpirole in both neuron types (e.g., the effect of 0.01 mu M quinpi role was reduced by approximate to 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 dopa mine D-2 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. (C ) 1999 IBRO. Published by Elsevier Science Ltd.