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

Mona Boules, Lewis Warrington, Abdul Fauq, Daniel McCormick, Elliott Richelson

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Parkinson's disease is a neuropathological disorder involving the degeneration of dopamine neurons in the substantia nigra, with the resultant loss of their terminals in the striatum. This dopamine loss causes most of the motor disturbances associated with the disease. One animal model of Parkinson's disease involves destruction of the nigrostriatal pathway with a neurotoxin (6-hydroxydopamine) injected into this pathway. In unilaterally lesioned animals, injection of D-amphetamine causes rotation towards the lesioned side, while injection of apomorphine acting upon supersensitive postsynaptic dopamine receptors causes rotation away from the lesioned side. In this study, we tested the effects of acute and subchronic injection of a neurotensin analog (NT69L) on the rotational behavior induced by D-amphetamine (5 mg/kg) or apomorphine (600 μg/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 contralateral rotation and D-amphetamine-induced ipsilateral rotation in these lesioned rats with an ED50 of 40 and 80 μg/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.

Original languageEnglish (US)
Pages (from-to)227-233
Number of pages7
JournalEuropean Journal of Pharmacology
Volume428
Issue number2
DOIs
StatePublished - Oct 5 2001

Keywords

  • 6-Hydroxydopamine
  • Neurotensin
  • Parkinson's disease

ASJC Scopus subject areas

  • Pharmacology

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