The use of serotonin type 7 receptor antagonists as a pharmacological intervention in chronic stress. Insights from animal studies

This mini-review presents our current understanding of serotonin type 7 receptor research focusing on the possible network mechanisms underlying the behavioral action of receptor antagonists. The serotonin type 7 receptor is expressed widely throughout the nervous system and known to be involved in various cognitive and physiological mechanisms. It became a clinically significant target after the discovery that its selective antagonist SB 269970 can exert rapid-onset antidepressant effects either alone or in combination with lower doses of conventional antidepressant drugs. Further research has shown that administration of SB 269970 can effectively counteract negative neurobiological outcomes in various chronic stress paradigms. The authors hope they can introduce a wider scientific audience to this promising pharmacological target which, if successful, could in time lead to more discoveries and a better understanding of the underlying serotonin receptor biology as well as its clinical potential.

Highlights

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  The 5-HT₇ receptor is widely distributed throughout the nervous system.

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  5-HT₇ receptor antagonist SB 269970 exerts rapid-onset antidepressant effects.

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  Antidepressant effects of SB 269970 occur via changes in dorsal raphe activity and subsequent cortical serotonin release.