Sibille, Etienne, Sarnyai, Zoltan, Benjamin, Daniel, Gal, Judit, Baker, Harriet, and Toth, Miklos (1997) Antisense inhibition of 5-hydroxytryptamine2a receptor induces an antidepressant-like effect in mice. Molecular Pharmacology, 52 (6). pp. 1056-1063.

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Abstract

Treatment with different antidepressants is invariably accompanied by the down-regulation of the 5-hydroxytryptamine2A(5-HT2A) receptor. To determine whether receptor down-regulation is an essential part of antidepressant action, we manipulated levels of the 5-HT2A receptor by using a nonpharmacological approach. Here, we report that down-regulation of the 5-HT2A receptor by intracerebroventricular injection of antisense oligonucleotides resulted in an antidepressant-like effect in mice. Animals with 5-HT2A receptor deficiency showed less immobility in the Porsolt's forced swim test, a well established animal model that is used to identify drugs with an antidepressant effect. The overall locomotor activity of the receptor-deficient animals was not altered, demonstrating the specificity of the behavioral change in the Porsolt's forced swim test. Reduced immobility in this test was accompanied by a greater c-Fos response in piriform cortex. Because 5-HT2A receptors have been localized on γ-aminobutyric acid interneurons, the inhibitory activity of these neurons may be impaired at low receptor levels, leading to a greater c-Fos response in the piriform cortex and increased mobility in the Porsolt's forced swim test. These experiments demonstrate that down-regulation of the 5-HT2Areceptor alone is sufficient to achieve an antidepressant-like effect in mice and suggest that receptor down-regulation may be an essential part of the antidepressant drug action.

Item ID:	35117
Item Type:	Article (Research - C1)
ISSN:	1521-0111
Date Deposited:	28 Aug 2014 06:15
FoR Codes:	11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110903 Central Nervous System @ 80% 17 PSYCHOLOGY AND COGNITIVE SCIENCES > 1701 Psychology > 170101 Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology) @ 20%
SEO Codes:	92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920111 Nervous System and Disorders @ 100%
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