RT Journal Article
SR Electronic
T1 Medial Hypothalamic 5-Hydroxytryptamine (5-HT)<sub>1A</sub> Receptors Regulate Neuroendocrine Responses to Stress and Exploratory Locomotor Activity: Application of Recombinant Adenovirus Containing 5-HT<sub>1A</sub> Sequences
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10868
OP 10877
DO 10.1523/JNEUROSCI.3223-04.2004
VO 24
IS 48
A1 Li, Qian
A1 Holmes, Andrew
A1 Ma, Li
A1 Van de Kar, Louis D.
A1 Garcia, Francisca
A1 Murphy, Dennis L.
YR 2004
UL http://www.jneurosci.org/content/24/48/10868.abstract
AB Our previous studies found that serotonin transporter (SERT) knock-out mice showed increased sensitivity to minor stress and increased anxiety-like behavior but reduced locomotor activity. These mice also showed decreased density of 5-hydroxytryptamine (5-HT1A) receptors in the hypothalamus, amygdala, and dorsal raphe. To evaluate the contribution of hypothalamic 5-HT1A receptors to these phenotypes of SERT knock-out mice, two studies were conducted. Recombinant adenoviruses containing 5-HT1A sense and antisense sequences (Ad-1AP-sense and Ad-1AP-antisense) were used to manipulate 5-HT1A receptors in the hypothalamus. The expression of the 5-HT1A genes is controlled by the 5-HT1A promoter, so that they are only expressed in 5-HT1A receptor-containing cells. (1) Injection of Ad-1AP-sense into the hypothalamus of SERT knock-out mice restored 5-HT1A receptors in the medial hypothalamus; this effect was accompanied by elimination of the exaggerated adrenocorticotropin responses to a saline injection (minor stress) and reduced locomotor activity but not by a change in increased exploratory anxiety-like behavior. (2) To further confirm the observation in SERT-/- mice, Ad-1AP-antisense was injected into the hypothalamus of normal mice. The density and the function of 5-HT1A receptors in the medial hypothalamus were significantly reduced in Ad-1AP-antisense-treated mice. Compared with the control group (injected with Ad-track), Ad-1A-antisense-treated mice showed a significant reduction in locomotor activity, but again no changes in exploratory anxiety-like behaviors, tested by elevated plus-maze and open-field tests. Thus, the present results demonstrate that medial hypothalamic 5-HT1A receptors regulate stress responses and locomotor activity but may not regulate exploratory anxiety-like behaviors.