Antisense Oligonucleotide‐Induced Reduction in 5‐Hydroxytryptamine7 Receptors in the Rat Hypothalamus Without Alteration in Exploratory Behaviour or Neuroendocrine Function

• Published in: Journal of neurochemistry 1998-09, Vol.71 (3), p.1271-1279
• Main Authors: Clemett, D. A., Cockett, M. I., Marsden, C. A., Fone, K. C. F.
• Format: Article
• Language: English
• Subjects: 5‐Hydroxytryptamine7 receptor; Animals; Antisense; Aversive behaviour; Behavior, Animal - drug effects; Behavioral psychophysiology; Biological and medical sciences; Body Weight - drug effects; Corticosterone - blood; Eating - drug effects; Exploratory Behavior - drug effects; Exploratory Behavior - physiology; Fundamental and applied biological sciences. Psychology; Hormones and behavior; Hypothalamic function; Hypothalamus - metabolism; Male; Maze Learning - drug effects; Neurosecretory Systems - physiology; Oligonucleotide; Oligonucleotides, Antisense - genetics; Oligonucleotides, Antisense - pharmacology; Prolactin - blood; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Inbred Strains; Receptors, Serotonin - genetics; Receptors, Serotonin - metabolism; Serotonin; Serotonin - metabolism; Time Factors
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1998.71031271.x

: The effect of a 5‐hydroxytryptamine7 (5‐HT7) receptor‐directed antisense oligonucleotide on rat behaviour and neuroendocrine function was investigated. Six days of intracerebroventricular 5‐HT7 antisense oligonucleotide treatment significantly reduced [3H]5‐HT binding to hypothalamic 5‐HT7 receptors, whereas cortical 5‐HT2C 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‐HT7 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‐HT7 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‐HT7 antisense oligonucleotide administration selectively reduced rat hypothalamic 5‐HT7 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‐HT7 receptor functions, and that this receptor is not critical for the control of neuroendocrine function or food intake.