A novel neurotensin analog blocks cocaine- and D-amphetamine-induced hyperactivity.
Neurotensin is a tridecapeptide that exhibits selective anatomic and neurochemical interactions with dopaminergic systems. Since dopaminergic neurotransmission underlies many of the behavioral properties of psychostimulants, and since neurotensin has been implicated in modulating dopaminergic neurotransmitter systems, we tested the effect of our novel neurotensin analog, NT69L (N-methyl-Arg(8),L-Lys(9),L-neo-Trp(11),tert-Leu(12)]neurotensin-(8-13)), on hyperactivity caused by cocaine and D-amphetamine. Previously, we showed that NT69L reduces body temperature, blocks apomorphine-induced climbing, and haloperidol-induced catalepsy. In this study, NT69L blocked the hyperactivity induced by both cocaine and D-amphetamine administered at three different doses each, when this peptide was injected intraperitoneally. These results provide further evidence for the involvement of the neurotensin system in some of the behavioral properties of psychostimulants and suggest that NT69L may find clinical application in patients who abuse this class of compounds.
Boules
M
M
Neuropsychopharmacology Laboratory, Mayo Foundation for Medical Education and Research, and Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA. Boules.mona@mayo.edu
Warrington
L
L
Fauq
A
A
McCormick
D
D
Richelson
E
E
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D010446:Peptide Fragments; C407426:neurotensin 69L; D009496:Neurotensin; D003042:Cocaine; D003913:Dextroamphetamine