title: The neurotensin receptor agonist NT69L suppresses sucrose-reinforced operant behavior in the rat.
abstract: NT69L is a neurotensin analog that can be administered peripherally. It blocks amphetamine- and cocaine-induced hyperactivity in rats. It also blocks nicotine-induced locomotor activity and has shown sustained efficacy in a rat model of nicotine-induced sensitization. The present study tested the effect of NT69L on responding for sucrose reinforcement on a continuous reinforcement schedule (CRF) and incrementing (FR1-FR5) discrimination schedule. Male Sprague-Dawley rats, on restricted food intake, were trained to press a lever for sucrose pellets on a CRF and incrementing discrimination schedule of reinforcement. On the following day, the testing session was followed by an extinction session, where lever pressing was not reinforced. Immediately after extinction, a reversal to CRF was implemented to test for relapse. Trained rats were injected with NT69L (1 mg/kg) or saline 30 min before each testing session. Dopamine, tyrosine 3-hydroxylase, and dopamine receptor mRNA levels were determined. NT69L significantly suppressed the lever pressing behavior for sucrose reinforcement on CRF which measures the "hedonic" value of the reward. NT69L also suppressed sucrose self-administration on the incrementing discrimination schedule of reinforcement (FR3-FR5) that is analogous to the motivational incentive. Reversal to CRF was significantly reduced by pretreatment with NT69L. The suppression of sucrose self-administration behavior by pretreatment with NT69L had a pattern similar to that for extinction. The effect of NT69L on dopamine, tyrosine 3-hydroxylase, and dopamine receptor mRNA levels is discussed relative to changes occurring during extinction.
authors.affiliation: Mayo Foundation for Medical Education and Research and Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA. boules.mona@mayo.edu
authors.forename: Mona
authors.initials: M
authors.lastname: Boules
authors.forename: Iver
authors.initials: I
authors.lastname: Iversen
authors.forename: Alfredo
authors.initials: A
authors.lastname: Oliveros
authors.forename: Amanda
authors.initials: A
authors.lastname: Shaw
authors.forename: Katrina
authors.initials: K
authors.lastname: Williams
authors.forename: Jessica
authors.initials: J
authors.lastname: Robinson
authors.forename: Paul
authors.initials: P
authors.lastname: Fredrickson
authors.forename: Elliott
authors.initials: E
authors.lastname: Richelson
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D005508:Food Deprivation / Q000502:physiology; D008297:Male; D009496:Neurotensin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism; D018028:Receptors, Neurotensin / Q000819:agonists / Q000378:metabolism*; D012054:Reinforcement, Psychology; D012646:Self Administration; D013395:Sucrose / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D018028:Receptors, Neurotensin; C407426:neurotensin 69L; D009496:Neurotensin; D013395:Sucrose; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine