Anxiogenic-like effects and reduced stereological counting of immunolabelled 5-hydroxytryptamine6 receptors in rat nucleus accumbens by antisense oligonucleotides.
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.
Otano
A
A
Department of Pharmacology, University of Navarra Medical School, Pamplona, Spain.
Frechilla
D
D
Cobreros
A
A
Cruz-Orive
L M
LM
Insausti
A
A
Insausti
R
R
Hamon
M
M
Del Rio
J
J
D000818:Animals; D001007:Anxiety / Q000209:etiology*; D001522:Behavior, Animal / Q000502:physiology; D007150:Immunohistochemistry; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D009714:Nucleus Accumbens / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
D016376:Oligonucleotides, Antisense; D011985:Receptors, Serotonin