Antiparkinson-like effects of a novel neurotensin analog in unilaterally 6-hydroxydopamine lesioned rats

Parkinson's disease is a neuropathological disorder involving the degenerat ion of dopamine neurons in the substantia nigra, with the resultant loss of their terminals in the striatum. This dopamine loss causes most of the mot or disturbances associated with the disease. One animal model of Parkinson' s disease involves destruction of the nigrostriatal pathway with a neurotox in (6-hydroxydopamine) injected into this pathway. In unilaterally lesioned animals, injection Of D-amphetamine causes rotation towards the lesioned s ide, while injection of apomorphine acting upon supersensitive postsynaptic dopamine receptors causes rotation away from the lesioned side. In this st udy, we tested the effects of acute and subchronic injection of a neurotens in analog (NT69L) on the rotational behavior induced by D-amphetamine (5 mg /kg) or apomorphine (600 mug/kg) in unilaterally 6-hydroxydopamine lesioned rats. Pretreatment of animals with intraperitoneal injections of NT69L (1 mg/kg) resulted in a significant reduction of apomorphine-induced contralat eral rotation and D-amphetamine-induced ipsilateral rotation in these lesio ned rats with an ED50 of 40 and 80 mug/kg, respectively. After three daily injections of NT69L, its effects on this rotational behavior were unchanged , suggesting that no tolerance develops to this effect of NT69L. (C) 2001 E lsevier Science B.V. All rights reserved.