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Anxiolytic effect and memory improvement in rats by antisense oligodeoxynucleotide to 5‐hydroxytryptamine‐ 2A precursor protein
Author(s) -
Cohen Hagit
Publication year - 2005
Publication title -
depression and anxiety
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.634
H-Index - 129
eISSN - 1520-6394
pISSN - 1091-4269
DOI - 10.1002/da.20087
Subject(s) - serotonergic , anxiolytic , elevated plus maze , serotonin , pharmacology , receptor , hippocampus , 5 ht receptor , downregulation and upregulation , morris water navigation task , psychology , chemistry , amnesia , anxiety , neuroscience , medicine , biochemistry , psychiatry , gene
Serotonergic (5‐hydroxytryptamine; 5‐HT) mechanisms have been implicated in a number of physiological and pathophysiological processes including mood, anxiety, and cognitive functioning. Among the many 5‐HT receptor subtypes, the 5‐HT 2A receptors (5‐HT 2A ‐R) seem to be of particular importance in mediating these effects, and they are prime targets for a variety of psychoactive substances—from hallucinogenic drugs, through atypical antipsychotics, to anxiolytics and antidepressants. Various selective 5‐HT 2A ‐R ligands induce different behavioral responses. To determine whether receptor downregulation is an essential part of anxiolytic action, levels of 5‐HT 2A receptors were manipulated in rats using a nonpharmacological approach—by the administration of an antisense oligodeoxynucleotide (ASODN) to 5‐HT 2A ‐R. Each ASODN was injected icv between two and five times at 24‐hr intervals. Control rats received injections of either a scrambled oligodeoxynucleotide (ScrODN) or the vehicle only. On Day 6, anxiety‐related behavior was assessed in the elevated plus maze paradigm and performance of memory tasks in the Morris water maze. Gene transcripts were measured by quantitative reverse transcription polymerase chain reaction (PCR). The results show that compared to vehicle and ScrODN control animals, icv 5‐HT 2A ‐R‐ASODN administrations for 4 consecutive days (but not less) significantly decreased anxietylike behavior and improved memory retention performance. The reduction in anxiety‐related behavior in 5‐HT 2A ‐R‐ASODN rats was accompanied by a decrease in 5‐HT 2A ‐R‐mRNA expression in the frontal cortex and in the hippocampus. Receptor downregulation has been proposed as one of the central mechanisms for anxiolytic drug actions. Antisense‐mediated downmanipulation of receptors in this study, especially of 5‐HT 2A , supports this theory. Depression and Anxiety 22:84–93, 2005. © 2005 Wiley‐Liss, Inc.