Effect of the 
3 adrenoceptor agonist CL 316243 on hypothalamic 5-HT
synthesis and suppression of REM sleep in the rat
R. K Conley*,
J Li,
M Ivarsson,
P. H Hutson
In Vivo Neuroscience Department, The Neuroscience Research Centre,
Merck Sharp and Dohme, Harlow, Essex, UK.
* To whom correspondence should be addressed.
 |
Abstract |
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3 adrenoceptor agonists show an antidepressant-like profile in preclinical
rodent assays and improve mood in clinically-obese patients. These observations
suggest a possible antidepressant utility for 3 adrenoceptor agonists. The
present study examined the effects of acute and chronic administration of the
3 adrenoceptor agonist CL 316243 on two physiological indicators of
antidepressant activity in the rat: hypothalamic 5-HT synthesis and suppression of
REM sleep. 5-HT synthesis was estimated by the accumulation of 5-hydroxytryptophan
(5-HTP) after treatment with the L-aromatic acid decarboxylase inhibitor NSD 1015.
Sleep-wake patterns were monitored using electroencephalogram and electromyogram
signals collected by radiotelemetry. Rats were administered CL 316243 acutely or
once daily for 11 days. Acute administration of CL 316243 significantly increased
hypothalamic 5-HT synthesis, as indicated by increased levels of 5-HTP, and reduced
the amount of REM sleep. However, chronic administration produced no changes in
5-HTP or REM compared with vehicle treatment. The present observations suggest that
acute administration of CL 316243 causes antidepressant-like effects on REM sleep,
possibly mediated by increased central 5-HT synthesis. However, these effects are
not maintained with repeated dosing.
Key Words:
3 adrenoceptor, REM sleep, 5-HT synthesis, hypothalamus, rat, depression
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