Neuroscience 2005 Abstract
| Presentation Number: | 114.5 |
|---|---|
| Abstract Title: | Activation of lateral hypothalamic orexin neurons reinstates morphine-seeking behavior. |
| Authors: |
Wimmer, M. E.*1
; Harris, G. C.1
; Aston-Jones, G.1
1Dept Psychiatry, Univ. of Pennsylvania, Philadelphia, PA |
| Primary Theme and Topics |
Disorders of the Nervous System - Addiction and Drugs of Abuse -- Neurobiology of reward |
| Secondary Theme and Topics | Disorders of the Nervous System<br />- Addiction and Drugs of Abuse<br />-- Learning, reward, and addiction |
| Session: |
114. Neurobiology of Reward Poster |
| Presentation Time: | Saturday, November 12, 2005 1:00 PM-2:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # VV88 |
| Keywords: | conditioned place preference, addiction, reward, opiate |
Orexin neurons in the lateral hypothalamus (LH) send projections to reward-associated brain areas including the nucleus accumbens and the ventral tegmental area (VTA), indicating a possible mechanism whereby LH stimulation could influence motivated behavior. Last year we reported that LH orexin neurons are stimulated (as measured by Fos induction) in proportion to the amount of preference shown for food-, cocaine- or morphine-associated cues during conditioned place preference (CPP) testing (Harris et al., SFN 2004). These findings were specific for orexin neurons located lateral to the fornix in the LH area but not for orexin neurons found medial to or surrounding the fornix. This data indicated that activation of orexin cells in the LH maybe involved in the preference (or craving) for reward-related cues. In the current studies, we found that microinjections of Y4 agonist, rat pancreatic polypeptide rPP, a potent stimulator of orexin cells; 0.045 nmol/side) into the LH reinstated an extinguished CPP for morphine, similar to a systemic injection of morphine. Reinstatement induced by rPP in the LH was blocked by pretreating the animals with a selective non-peptide Orexin-1 receptor antagonist (SB 334867; 30mg/Kg). This finding indicates that the reinstatement effect was mediated by orexin. We also found a significant positive correlation between the number of Fos+ orexin cells in the LH following the rPP microinjections and the reinstatement score. Direct microinjections of orexin A (140 nM) into the VTA also reinstated extinguished morphine preference. Together, these data indicate that orexin cells in the LH are not only stimulated by drug-associated cues but may also play a role in reinstatement of drug seeking behavior. Our preliminary data indicate that LH orexin neurons are activated during morphine conditioning and further experiments are being conducted to assess the role of the LH orexin system in the acquisition and expression of morphine CPP.
Supported by PHS grant DA06214
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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