Antisense oligodeoxynucleotides against the MOR-1 clone alter weight and ingestive responses in rats Journal Article


Authors: Leventhal, L.; Cole, J. L.; Rossi, G. C.; Pan, Y. X.; Pasternak, G. W.; Bodnar, R. J.
Article Title: Antisense oligodeoxynucleotides against the MOR-1 clone alter weight and ingestive responses in rats
Abstract: MOR-1 encodes a μ receptor. In an effort to establish the relationship of this cloned opioid receptor with ingestive behavior and analgesia in rats, the present study examined the actions of four antisense oligodeoxynucleotides aimed at exons 1 (AS1), 2 (AS2), 3 (AS3) and 4 (AS4) of the MOR-1 clone, as well as a mismatch antisense sequence (MS1). Rats were administered intracerebroventricular injections (10 μg/2 μl) of each of the oligodeoxynucleotides on days 1, 3 and 5. Body weight and spontaneous food and water intake were monitored daily. In addition, 2-deoxy-D-glucose (2DG)-induced hyperphagia, central Angiotensin II (ANG-II)-induced hyperdipsia and central morphine analgesia were examined 24 h following the last antisense injection. AS1, AS2, AS3 and AS4 each significantly reduced body weight (7-17 g), food intake (8-13 g) and water intake (11-23 ml), while the vehicle or MS1 conditions significantly increased weight (9-20 g) and produced smaller reductions (2-4 g) in food intake. None of the AS probes altered the magnitude of either 2DG-induced hyperphagia or ANG-II-induced hyperdipsia. Central morphine-analgesia was reduced by pretreatment with AS1 and AS4, but not AS2, AS3 or MS1. The sensitivity of general feeding to all four exons suggest that the receptor responsible for this action is encoded by the MOR-1 clone. The differences between feeding and morphine analgesia raise the possibility that these two actions are mediated through different μ receptor subtypes. Our results also demonstrate the viability of the in vivo antisense technique in modulating opioid-mediated ingestive responses.
Keywords: controlled study; nonhuman; animal experiment; food intake; angiotensin ii; rat; behavior; morphine; opioid; analgesia; fluid intake; mu opiate receptor; receptor subtype; antisense oligodeoxynucleotide; morphine analgesia; intracerebroventricular drug administration; μ opioid receptor; male; priority journal; article; angiotensin; glucoprivation
Journal Title: Brain Research
Volume: 719
Issue: 1-2
ISSN: 0006-8993
Publisher: Elsevier Science, Inc.  
Date Published: 1996-05-06
Start Page: 78
End Page: 84
Language: English
DOI: 10.1016/0006-8993(96)00089-3
PUBMED: 8782866
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 22 November 2017 -- Source: Scopus
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MSK Authors
  1. Yingxian Pan
    132 Pan
  2. Grace Rossi
    61 Rossi
  3. Gavril W Pasternak
    414 Pasternak