title: Effect of a novel neurotensin analog, NT69L, on nicotine-induced alterations in monoamine levels in rat brain.
abstract: NT69L, is a novel neurotensin (8-13) analog that participates in the modulation of the dopaminergic pathways implicated in addiction to psychostimulants. NT69L blocks nicotine-induced hyperactivity as well as the initiation and expression of sensitization in rats. Recent evidence suggests that stimulation of mesocorticolimbic dopamine system, with influences from the other monoamine systems, e.g. norepinephrine and serotonin, is involved in nicotine's reinforcing properties. The aim of the present study was to investigate the effect of pretreatment with NT69L on nicotine-induced changes in monoamine levels in the rat brain using in vivo microdialysis. Acute or chronic (0.4 mg/kg, sc, once daily for 2 weeks) administration of nicotine elicited increases in extracellular levels of dopamine, dopamine metabolites, norepinephrine, or serotonin in medial prefrontal cortex, nucleus accumbens shell, and core of rats. Pretreatment with NT69L (1 mg/kg, intraperitoneally, ip) administered 40 min before nicotine injection significantly attenuated the acute nicotine-evoked increases in norepinephrine levels in medial prefrontal cortex, dopamine and serotonin in nucleus accumbens shell. After chronic nicotine administration, pretreatment of NT69L markedly reversed the increase in dopamine levels in the nucleus accumbens core. NT69L's attenuation of some of the biochemical effects of acute and chronic nicotine is consistent with this peptide's attenuation of nicotine-induced behavioral effects. These data further support a role for NT69L or other neurotensin receptor agonists to treat nicotine addiction.
authors.affiliation: Neuropsychopharmacology Laboratory and Nicotine Dependence Center, Mayo Foundation for Medical Education and Research, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA. liang.yanqi@mayo.edu
authors.forename: Yanqi
authors.initials: Y
authors.lastname: Liang
authors.forename: Mona
authors.initials: M
authors.lastname: Boules
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Shaw
authors.forename: Katrina
authors.initials: K
authors.lastname: Williams
authors.forename: Paul
authors.initials: P
authors.lastname: Fredrickson
authors.forename: Elliott
authors.initials: E
authors.lastname: Richelson
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D017551:Microdialysis; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009496:Neurotensin / Q000819:agonists* / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D009638:Norepinephrine / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D014029:Tobacco Use Disorder / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
chemical_list: D015306:Biogenic Monoamines; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D010446:Peptide Fragments; C407426:neurotensin 69L; D012701:Serotonin; D009496:Neurotensin; D009538:Nicotine; D004298:Dopamine; D009638:Norepinephrine