PT  - JOURNAL ARTICLE
AU  - Qian Li
AU  - Andrew Holmes
AU  - Li Ma
AU  - Louis D. Van de Kar
AU  - Francisca Garcia
AU  - Dennis L. Murphy
TI  - 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
AID  - 10.1523/JNEUROSCI.3223-04.2004
DP  - 2004 Dec 01
TA  - The Journal of Neuroscience
PG  - 10868--10877
VI  - 24
IP  - 48
4099  - http://www.jneurosci.org/content/24/48/10868.short
4100  - http://www.jneurosci.org/content/24/48/10868.full
SO  - J. Neurosci.2004 Dec 01; 24
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.