The ACTH-(4–9) analogue ORG 2766 facilitates denervation supersensitivity after a unilateral 6-OHDA lesion of the corpus striatum in rats

Abstract

Direct bilateral 6-OHDA lesioning of the nucleus accumbens causes a temporary reduction in motility, followed by a spontaneous recovery in 3–4 weeks. The ACTH-(4–9) analogue ORG 2766 shortens this period to 1 week. The functional and the peptide-induced facilitation of recovery are accompanied by enhanced motility upon administration of the dopamine agonist apomorphine which may be related to denervation supersensitivity. The present experiments were performed to investigate the interaction between ORG 2766 and denervation supersensitivity in another dopaminergic terminal area i.e. the corpus striatum. After a unilateral 6-OHDA lesion of the right corpus striatum, contralateral rotation was observed upon administration of a high dose of apomorphine 2, 3 and 4 weeks after the lesion, indicating supersensitivity of postsynaptic dopaminergic receptor systems. Contralateral rotation upon administration of this dose of apomorphine was observed in ORG 2766 treated animals, already at 1 week after the lesion. Peptide treatment resulted in an enhanced sensitivity for apomorphine, since contralateral rotation was observed in peptide but not in placebo treated, 6-OHDA lesioned animals after a low dose of apomorphine. In conclusion: treatment with ORG 2766 facilitates the development of denervation supersensitivity and enhances sensitivity for apomorphine probably through an increased affinity of dopaminergic receptors for domapine agonists.