Antisense oligonucleotide-induced reduction in 5-hydroxytryptamine7 receptors in the rat hypothalamus without alteration in exploratory behaviour or neuroendocrine function.
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.
Clemett
D A
DA
School of Biomedical Sciences, Queen's Medical Centre, Nottingham University, England, UK.
Cockett
M I
MI
Marsden
C A
CA
Fone
K C
KC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004435:Eating / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009490:Neurosecretory Systems / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000235:genetics* / Q000494:pharmacology; D011388:Prolactin / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
D016376:Oligonucleotides, Antisense; D011985:Receptors, Serotonin; D012701:Serotonin; D011388:Prolactin; D003345:Corticosterone