EVIDENCE FOR VOLUME TRANSMISSION IN THE DOPAMINE DENERVATED NEOSTRIATUM OF THE RAT AFTER A UNILATERAL NIGRAL 6-OHDA MICROINJECTION - STUDIES WITH SYSTEMIC D-AMPHETAMINE TREATMENT

In the present study the hypothesis has been tested if the dopamine re leasing drug D-amphetamine via volume transmission can, at least partl y, restore dopamine communication in the dopaminergically denervated n eostriatum of rats. The experimental model used, has been a unilateral 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine neurons, based on nigral microinjections of this neurotoxin. Studies o n c-fos like immunoreactivity after systemic D-amphetamine treatment d emonstrated a wide-spread appearance of c-fos like immunoreactive neur onal nuclear profiles within the neostriatum on both the unlesioned an d denervated side. In the unlesioned neostriatum a peak density of c-f os like immunoreactive profiles was found within the central part of t he neostriatum, while on the denervated side the distribution pattern of c-fos like immunoreactive profiles peaked medially and gradually de clined in a lateral direction. The microdialysis experiments demonstra ted, after systemic d-amphetamine treatment, a marked and sustained in crease of extracellular dopamine levels in the neostriatum on the unle sioned side, while no increases in the extracellular dopamine levels w ere observed on the dopaminergically denervated neostriatum. In the el ectrophysiological experiments, systemic D-amphetamine treatment produ ced an inhibition of the neuronal activity on the denervated side whic h showed a significant increase in basal discharge rate compared with the recordings obtained from the striata on the unlesioned side. The p resent immunocytochemical microdialysis and electrophysiological analy sis provides evidence that in the unilaterally markedly dopamine deple ted neostriatum with clearcut signs of dopamine receptor supersensitiv ity (rotational behaviour results), dopamine transmission may be partl y restored via systemic D-amphetamine treatment through the release of dopamine, predominantly from the unlesioned neostriatum, which may di ffuse into the cerebrospinal fluid to reach the contralateral dopamine rgically denervated neostriatum.