Effects of neurotensin in a rodent model of tardive dyskinesia.
The role of neurotensin (NT) in a putative model of tardive dyskinesia (TD) was examined in the rat. When administered directly into the ventrolateral striatum of neuroleptic-naive animals, NT (2.5 micrograms/side) elicited vacuous chewing movements. This response was not seen following administration of NT into other striatal regions or the substantia nigra and was suppressed by the NT antagonist SR 48692 (100 micrograms/kg i.p.). Vacuous chewing movements were also seen following chronic administration of fluphenazine decanoate. These movements were likewise suppressed by SR 48692 (10-100 micrograms/kg i.p.), which failed to affect other behavioural responses and was without effect in neuroleptic-naive animals. Our data suggest that increased levels of endogenous NT within the ventrolateral striatum may play a critical role in the development of TD following chronic neuroleptic administration and that NT antagonists may be beneficial for the treatment of this disorder.
Stoessl
A J
AJ
Department of Clinical Neurological Sciences, University of Western Ontario, London, Canada.
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000209:etiology*; D005476:Fluphenazine / Q000494:pharmacology; D008297:Male; D009496:Neurotensin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors*; D013378:Substantia Nigra / Q000187:drug effects*
D018028:Receptors, Neurotensin; D009496:Neurotensin; D005476:Fluphenazine