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Abstract: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-HT 7 receptors, whereas cortical 5-HT2~density remained unchanged. In rats on a foodrestricted 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. Key Words: 5-Hydroxytryptamine7 receptor-Serotonin-Antisense-Oligonucleotide-Hypothalamic function -Aversive behaviour.

1 Pindolol-insensitive [ 3 H]-5-hydroxytryptamine ([ 3 H]-5-HT) binding to rat hypothalamic membranes was pharmacologically and functionally characterized to resolve whether this procedure selectively labels 5-HT 7 receptors. 2 Consistent with a previous report, 3 mM and not 100 nM pindolol was required to occupy fully 5-HT 1A and 5-HT 1B receptors. Remaining