TY - JOUR
T1 - Antiparkinson-like effects of a novel neurotensin analog in unilaterally 6-hydroxydopamine lesioned rats
AU - Boules, Mona
AU - Warrington, Lewis
AU - Fauq, Abdul
AU - McCormick, Daniel
AU - Richelson, Elliott
N1 - Funding Information:
This work was funded by grant MH 27692 from the National Institute of Mental Health, the Forrest C. Lattner Foundation and by the Mayo Foundation for Medical Education and Research.
PY - 2001/10/5
Y1 - 2001/10/5
N2 - 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.
AB - 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.
KW - 6-Hydroxydopamine
KW - Neurotensin
KW - Parkinson's disease
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U2 - 10.1016/S0014-2999(01)01260-2
DO - 10.1016/S0014-2999(01)01260-2
M3 - Article
C2 - 11675040
AN - SCOPUS:0035812650
SN - 0014-2999
VL - 428
SP - 227
EP - 233
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2
ER -