Behavioural and Biochemical Studies With the Benzamide Sulpiride in Rats

Abstract

We have studied the effects of the benzamide, sulpiride, on dopamine transmission using a functional approach combining brain dialysis experiments with behavioural studies utilising rotational and holeboard models. In the 6-OH-dopamine-rotational model, both apomorphine and pergolide induced a dose-dependent contralateral rotation. However, sulpiride blocks very effectively the pergolide responses whilst it inhibits poorly the apomorphine rotation. Further studies using the same model suggest different receptor mechanisms distinctly distributed in the striata of rats and involving different efferent pathways. A dialysis tube was implanted into the left striatum of rats in order to study changes in dopamine release after influencing dopamine autoreceptors. Apomorphine produced a decrease of dopamine release which was reversed by sulpiride. The dopamine autoreceptor regulation of exploratory behaviour has been studied using an automatic holeboard device. Apomorphine and pergolide inhibited locomotion in an dose-dependent manner. This inhibition was selectively reversed by sulpiride but not by cis-flupenthixol. The dialysis provided also another possibility to study the functional regulation of DA systems. It has been suggested that sulpiride most effectively blocks the dopamine receptors localized presynaptically on cortico-striatal glutamate afferent neurons. We have compared the effects of cis-flupenthixol and sulpiride on glutamate and GABA release as measured by dialysis in the striata of rats. We found no clearcut effect after cis-flupenthixol, while sulpiride caused a significant change in glutamate release.