Abstract
In the present study the hypothesis has been tested if the dopamine releasing drug d-amphetamine via volume transmission can, at least partly, restore dopamine communication in the dopaminergically denervated neostriatum 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 on c-fos like immunoreactivity after systemic d-amphetamine treatment demonstrated a wide-spread appearance of c-fos like immunoreactive neuronal nuclear profiles within the neostriatum on both the unlesioned and denervated side. In the unlesioned neostriatum a peak density of c-fos like immunoreactive profiles was found within the central part of the neostriatum, while on the denervated side the distribution pattern of c-fos like immunoreactive profiles peaked medially and gradually declined in a lateral direction. The microdialysis experiments demonstrated, after systemic d-amphetamine treatment, a marked and sustained increase of extracellular dopamine levels in the neostriatum on the unlesioned side, while no increases in the extracellular dopamine levels were observed on the dopaminergically denervated neostriatum. In the electrophysiological experiments, systemic d-amphetamine treatment produced an inhibition of the neuronal activity on the denervated side which showed a significant increase in basal discharge rate compared with the recordings obtained from the striata on the unlesioned side. The present immunocytochemical microdialysis and electrophysiological analysis provides evidence that in the unilaterally markedly dopamine depleted neostriatum with clearcut signs of dopamine receptor supersensitivity (rotational behaviour results), dopamine transmission may be partly restored via systemic d-amphetamine treatment through the release of dopamine, predominantly from the unlesioned neostriatum, which may diffuse into the cerebrospinal fluid to reach the contralateral dopaminergically denervated neostriatum.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
