RT Journal Article
SR Electronic
T1 Determination of the role of the 5-ht6 receptor in the rat brain: a study using antisense oligonucleotides.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 173
OP 180
VO 274
IS 1
A1 A Bourson
A1 E Borroni
A1 R H Austin
A1 F J Monsma, Jr
A1 A J Sleight
YR 1995
UL http://jpet.aspetjournals.org/content/274/1/173.abstract
AB The purpose of the present study was to determine possible physiological functions of the 5-ht6 receptor using antisense oligonucleotides (AOs) in male rats. Repeated intracerebroventricular treatment with AOs but not with a scrambled form of the antisense sequence (SO) gave rise to a specific behavioral syndrome of yawning, stretching and chewing and caused a 30% reduction in the number of [3H]-lysergic acid diethylamide binding sites (measured in the presence of 300 nM spiperone). Neither sequence, however, had any effect on other parameters measured (e.g., locomotor activity, body weight, food intake, body temperature and nociception). The specific behavioral syndrome did not appear to be caused by modulation of dopaminergic neurotransmission since no changes in the tissue levels of either dopamine or its metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were seen. Furthermore, haloperidol (0.03 mg/kg s.c.) did not reduce the number of yawns or stretches. An increase in cholinergic neurotransmission did appear to be involved since the behavioral syndrome was dose-dependently antagonized by atropine. The present study suggests that 5-ht6 receptors are functionally expressed in the rat brain, where one of their functions appears to be the control of cholinergic neurotransmission.