Neurotensin and neurotensin analogues modify the effects of chronic neuroleptic administration in the rat.
The effects of intracerebroventricular neurotensin and the neurotensin analogues neuromedin N and [D-Trp 11]neurotensin on the behavioural responses to chronic neuroleptic administration were investigated in the rat. Chronic (18 weeks) administration of a low dose (12.5 mg/kg, i.m., every 3 weeks) of fluphenazine decanoate alone failed to elicit the vacuous chewing mouth movements (VCMs) which have previously been reported following higher doses of this drug, but VCMs were seen in neuroleptic-treated animals following the additional administration of neurotensin. A higher dose of fluphenazine (25 mg/kg, i.m., every 3 weeks) greatly increased the VCM response, and this potentiation was suppressed to control levels by [D-Trp11]neurotensin, but unaffected by neuromedin N. These findings suggest that alterations in neurotensin may contribute to the deleterious extrapyramidal effects of long-term neuroleptic administration, and that [D-Trp11]neurotensin may attenuate these effects by blockade of neurotensin receptors within the central nervous system.
Department of Clinical Neurological Sciences, University of Western Ontario, Canada.
A J
AJ
Stoessl
E
E
Szczutkowski
D000818:Animals; D014150:Antipsychotic Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004357:Drug Synergism; D004409:Dyskinesia, Drug-Induced / Q000523:psychology*; D005476:Fluphenazine / Q000037:antagonists & inhibitors / Q000633:toxicity; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors
D014150:Antipsychotic Agents; D010446:Peptide Fragments; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter; C042090:neuromedin N; D009496:Neurotensin; C024309:neurotensin, Trp(11)-; D005476:Fluphenazine