Within the CNS and in the periphery, serotonin (5-HT) participates in a number of functions including cognition, mood, sleep-wake rhythms, intestinal inflammation. 5-HT receptors can be classified into at least seven classes, designated 5-HT1 to 5-HT7. Since its identification, the 5-HT7 receptor has been the subject of intense research efforts, driven by its presence in functionally-relevant brain regions and in the gut. The availability of selective agonists and antagonists, in combination with genetically-modified mice lacking 5-HT7 receptors, has allowed so far a better understanding about the patho-physiological roles of this receptor. This Topic will review the state-of-the-art from studies conducted in laboratory (alive animals, tissues, cells) on this respect: 1) Emerging preclinical evidence supports a role for the 5-HT7 receptor in depression, since its pharmacological blockade or genetic inactivation induce an antidepressant-like behavioural profile. 2) In addition, agonists and/or antagonists of 5-HT7 receptors may improve memory or reverse amnesia, having pro-mnesic and/or anti-amnesic effects, with therapy potential in disease-related and/or age-related cognitive impairment. 3) When adolescent rats are treated with a 5-HT7 agonist, analysis at adulthood shows an improved exploratory motivation / attentional skill as well as increased strength of connectivity among components of a forebrain “limbic” loop. The role of neuro-plasticity and the links to neuro-inflammatory processes will also be addressed. Therapeutic potential of the beneficial effects triggered by 5-HT7 stimulation warrant future research.
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