The novel neuropeptide Y Y5 receptor antagonist, Lu AA33810, attenuates food deprivation-induced reinstatement of heroin seeking
Monday, Nov 15, 2010, 8:00 AM - 9:00 AM
, T. MARIC
, M. W. WALKER
, F. SEDKI
Concordia Univ., Montreal, QC, Canada;
Lundbeck Research, USA, Paramus, NJ
Neuropeptide Y (NPY) is a 36-amino acid neurotransmitter that is released during periods of food deprivation (FD) and serves as an orexigenic signal that powerfully stimulates feeding via Y1 and Y5 receptor subtypes. We have recently demonstrated that central infusions of NPY facilitate both heroin and cocaine self-administration, enhance the locomotor activating properties of cocaine, and elicit the reinstatement of previously extinguished heroin-reinforced behavior in an animal model of relapse to drug abuse. Previously, we reported that FD-induced reinstatement of heroin seeking is blocked by the anorexigenic hormone, leptin. We hypothesized that leptin’s effect was mediated through its modulating effect on NPY release in the brain. However, we found that the NPY Y5 receptor antagonist, L152-804 (20.0 μg, i.c.v.), failed to block FD-induced reinstatement of heroin seeking. Recently, a novel NPY Y5 receptor antagonist, Lu AA33810, has been introduced, with high specificity to the Y5 receptor, and anxiolytic-like and antidepressant-like effects in rats. Here we examined the effects of Lu AA33810 on acute food deprivation-induced reinstatement of heroin seeking behavior.
Material and Methods
Long Evans male rats were trained to self-administer heroin (0.10 mg/kg/infusion, i.v.) over a period of 10 days (three 3-hr sessions/day) on a fixed-ratio 1 schedule of reinforcement. Heroin self-administration training was followed by a minimum of 4 days of extinction training. Subsequently, rats were exposed to two counterbalanced reinstatement test sessions, that consisted of 3-hr sessions under extinction conditions, which were preceded by either 21 hr FD or 21 hr of unlimited access to food. Rats received injections of the novel NPY Y5 receptor antagonist (Lu AA33810; 0.0, or 30.0 mg/kg/rat, i.p.) 30 min before each test.
The NPY Y5 receptor antagonist, Lu AA33810, significantly attenuated food deprivation-induced reinstatement of heroin seeking behavior (lever presses) in the absence of the drug.
Our preliminary results indicate that blocking the NPY Y5 receptor subtype, using a dose known to inhibit Y5 agonist-induced feeding, attenuates acute food deprivation-induced reinstatement of heroin seeking. We suggest that activation of the NPY Y5 receptors is critically involved in FD-induced reinstatement of drug seeking. Further research is currently being conducted in order to reveal the effective dose-range for Lu AA33810, and its effects on reinstatement induce by other known triggers for relapse, namely, drug-associated cues and priming.
Employment; Lundbeck Research USA.
NSERC Discovery Grant 298915
Canada Research Chair (CRC) Program
Fonds de la recherche en sante Quebec (FRSQ)
[Authors]. [Abstract Title]. Program No. XXX.XX. 2010 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2010. Online.
2010 Copyright by the Society for Neuroscience all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
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