Role of the dendritic release of dopamine in the reciprocal control of the two nigro-striatal dopaminergic pathways

USING cats implanted with push–pull cannulae, we have previously demonstrated a reciprocal regulation of the activity of the two nigro-striatal dopaminergic pathways. Asymmetric fluctuations in the spontaneous release of dopamine(DA) were simultaneously seen in the two caudate nuclei (CN)1. As revealed by the changes in DA release from nerve terminals, the unilateral nigral application of DA1 or of drugs enhancing the dendritic release of DA, such as amphetamine or benztropine (2), reduced the activity of ipsilateral dopaminergic neurones and induced an opposite effect in the contralateral side. Conversely, the unilateral nigral blockade of dopaminergic transmission by local application of neuroleptics enhanced the release of DA in the ipsilateral CN and decreased the transmitter release in the contralateral structure2. Opposite changes in the release of DA were also seen in the two CN under unilateral delivery of sensory stimuli3 or during unilateral electrical stimulation of the cerebellar dentate nucleus4. These latter effects were associated with asymmetric changes in the dendritic release of DA in the two substantia nigrae (SN) which were in an opposite direction to those seen in the two CN (an increased release of DA from nerve terminals corresponded to a decreased release of the transmitter from dendrites and vice versa). These experiments indicated that DA which is released from dendrites in one SN regulates the activity of the ipsilateral dopaminergic neurones; they also suggested that it contributes to the control of the contralateral dopaminergic neurones by influencing the dendritic release of DA in the contralateral SN. This hypothesis was confirmed in the present study by measuring the changes in DA release from nerve terminals and dendrites of the two pathways under pharmacological blockade or facilitation of dopaminergic transmission in one SN.