5-HT1B receptor mRNA levels in dorsal raphe nucleus: inverse association with anxiety behavior in the elevated plus maze.
Serotonergic neurons in the dorsal raphe nucleus, the major source of forebrain serotonin projections, synthesize a terminal autoreceptor that inhibits serotonin release-the 5-HT(1B) autoreceptor. Overexpression of this autoreceptor is hypothesized to contribute to anxiety. Antidepressants decrease (while learned helplessness increases) 5-HT(1B) mRNA in dorsal raphe neurons, and viral-mediated overexpression of 5-HT(1B) here increases anxiety behavior after stress. However, 5-HT(1B) mRNA levels in dorsal raphe are substantially elevated in unstressed rats in two models of stress resistance. Thus, the role of dorsal raphe 5-HT(1B) autoreceptors in anxiety is complex. Therefore, we tested whether different stressors differentially affect dorsal raphe 5-HT(1B) mRNA [via in situ hybridization histochemistry] and anxiety behavior (using the elevated plus maze). Rats were assigned to a stressor (either forced swim, water restraint, dry restraint, or electric tail shock) or a control condition, then were tested and sacrificed 24 h later. Overall, controls exhibited less anxiety than stressed rats as indicated by a higher ratio of open arm to total arm entries (OTR). The stressors did not differentially affect the OTR, nor did any alter dorsal raphe 5-HT(1B) mRNA levels. There was, however, a significant positive correlation between the OTR and 5HT(1B) mRNA intensity in controls (r=.64; P=.006), but not in stressed rats (r=.16, P=.36), providing further evidence that elevated dorsal raphe 5-HT(1B) levels are associated with reduced anxiety in animals that have not been exposed to stress.
Kaiyala
Karl J
KJ
Department of Psychiatry and Behavioral Sciences and Harborview Medical Center, University of Washington, Seattle, WA 98195, USA.
Vincow
Evelyn S
ES
Sexton
Timothy J
TJ
Neumaier
John F
JF
D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D011903:Raphe Nuclei / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B / Q000096:biosynthesis*
D012333:RNA, Messenger; D044302:Receptor, Serotonin, 5-HT1B