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Antisense Oligonucleotide‐Induced Reduction in 5‐Hydroxytryptamine 7 Receptors in the Rat Hypothalamus Without Alteration in Exploratory Behaviour or Neuroendocrine Function
Author(s) -
Clemett D. A.,
Cockett M. I.,
Marsden C. A.,
Fone K. C. F.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71031271.x
Subject(s) - receptor , endocrinology , hypothalamus , medicine , oligonucleotide , biology , serotonin , chemistry , biochemistry , dna
Abstract: The effect of a 5‐hydroxytryptamine 7 (5‐HT 7 ) receptor‐directed antisense oligonucleotide on rat behaviour and neuroendocrine function was investigated. Six days of intracerebroventricular 5‐HT 7 antisense oligonucleotide treatment significantly reduced [ 3 H]5‐HT binding to hypothalamic 5‐HT 7 receptors, whereas cortical 5‐HT 2C density remained unchanged. In rats on a food‐restricted diet, both antisense and mismatch oligonucleotides reduced food intake and body weight compared with that in vehicle‐treated controls by day 4 of administration. 5‐HT 7 antisense oligonucleotide administration did not affect exploratory or locomotor activity in photocell activity monitors on day 4 or elevated plus‐maze behaviour on day 6 of intracerebroventricular treatment. 5‐HT 7 antisense oligonucleotide did not affect plasma corticosterone or prolactin levels or 5‐HT turnover in either 5‐HT cell body or terminal areas. These data demonstrate that intracerebroventricular 5‐HT 7 antisense oligonucleotide administration selectively reduced rat hypothalamic 5‐HT 7 receptor density without affecting any of the biochemical or behavioural measures. The results suggest that this antisense protocol could be a valuable tool to investigate central 5‐HT 7 receptor functions, and that this receptor is not critical for the control of neuroendocrine function or food intake.