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The nature of the synaptic transmitter involved in the excitatory fibers linking the nucleus tegmenti pedunculopontinus (PPN) to the pars compacta of the substantia nigra (SNPC) was investigated using microiontophoretic techniques in rats anesthetized with ketamine. Among the SNPC cells activated orthodromically by PPN electrical stimulation, only a few cells were weakly excited by iontophoretically administered acetylcholine (Ach) while most were not affected. Conversely all cells were promptly and powerfully excited by short pulses of glutamate (GLU). The administration of the GLU antagonists glutamic acid diethyl ester (GDEE) and D-alpha-aminoadipic acid (DAA) reversibly and simultaneously suppressed both the PPN-evoked orthodromic response and the GLU-induced excitation of SNPC cells without affecting their response to iontophoretic Ach. GDEE was more effective than DAA in counteracting the synaptically evoked excitation. On the other hand, atropine, while antagonizing the Ach response in those cells which were cholinoceptive, did not affect either the PPN-evoked or the GLU-induced excitation. Hence, despite the presence of cholinergic cells in the PPN region, Ach does not appear to be involved in the excitatory PPN-SNPC pathway. The present findings suggest that the excitatory PPN fibers innervating the SNPC may utilize GLU or a closely related amino acid as a neurotransmitter.

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The effects of 6-hydroxydopamine (6-OHDA, 8 μ g) retrograde selective lesions of bilateral dopaminergic pathways, projecting from the ventral tegmental area of Tsai (VTA-A10) to the hippocampal formation (HF), were studied through assessment of male Sprague-Dawley rats behavior, before and following amphetamine challenge (day 15 and day 30, respectively after 6-OHDA injections). Significant differences in locomotor and exploratory activities and motor coordination were evidenced between and within groups by one-way analysis of variance (ANOVA). These VTA-hippocampal dopaminergic pathway lesions may provide a morphological basis for the interpretation of the psychomotor deficits shown in this study.