Repeated administration of the neurotensin analogue NT69L induces tolerance to its suppressant effect on conditioned avoidance behaviour.
Although acute neurotensin receptor stimulation exerts diverse behavioural effects that resemble those seen after administration of antipsychotic drugs, data on effects after repeated exposure to neurotensin receptor agonism is relatively sparse. Here, we demonstrate that repeated administration of the novel neurotensin-(8-13) analogue NT69L [(N-methyl-Arg), Lys, Pro, L-neo-Trp, tert-Leu, Leu] induce tolerance to its suppressant effect on conditioned avoidance behaviour in rats, a predictive assay for antipsychotic activity. In contrast, the inhibitory effect of haloperidol on this behaviour was sustained despite repeated administration of this classical antipsychotic drug. These findings indicate that repeated exposure to neurotensin receptor stimulation induces tolerance to the antipsychotic-like effects of neurotensin receptor agonists.
Hertel
Peter
P
Psychopharmacological Research, H. Lundbeck A/S, Ottiliavej 9, DK-2500 -Valby, Copenhagen, Denmark. phe@lundbeck.com
Olsen
Christina Kurre
CK
Arnt
Jørn
J
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D014150:Antipsychotic Agents; D010446:Peptide Fragments; C407426:neurotensin 69L; D009496:Neurotensin; D006220:Haloperidol