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Anxiogenic-like effects and reduced stereological counting of immunolabelled 5-hydroxytryptamine6 receptors in rat nucleus accumbens by antisense oligonucleotides.

Abstract：

:The physiological role of 5-hydroxytryptamine6 receptors in the central nervous system has not yet been elucidated. The high affinity of various psychotropic drugs for 5-hydroxytryptamine6 receptors has led to the suggestion that this receptor type may be a novel target in neuropsychiatry. We have found that continuous intracerebroventricular administration of a 5-hydroxytryptamine6 receptor antisense oligonucleotide, but not of a missense oligonucleotide, produced an anxiogenic-like response in rats using two different models of anxiety, the social interaction test and the elevated plus-maze. Neither oligonucleotide treatment modified locomotor activity, rectal temperature or food intake, suggesting a low or null neurotoxicity. The effectiveness of the treatment with the designed antisense oligonucleotide to block the synthesis of the protein encoded by the target mRNA was assessed by immunolabelling 5-hydroxytryptamine6 receptors in the nucleus accumbens, where this receptor is highly expressed, using previously characterized specific antibodies. The density of the immunostaining was quantified by means of an unbiased three-dimensional stereologic procedure, which revealed a significant reduction (-25%) in the number of immunolabelled neuronal elements. These results suggest that, in addition to other 5-hydroxytryptamine receptor subtypes, 5-hydroxytryptamine6 receptors in the nucleus accumbens may participate in anxiety-related neurobiological mechanisms.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Otano A,Frechilla D,Cobreros A,Cruz-Orive LM,Insausti A,Insausti R,Hamon M,Del Rio J

doi

10.1016/s0306-4522(99)00066-4

keywords:

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

1001-9

issue

3

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(99)00066-4

journal_volume

92

pub_type

杂志文章

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