Abstract
Pharmacological and genetic studies have implicated the mu opioid receptor (MOR) in the regulation of ethanol intake in animal models and humans. Non-specific antagonists of opioid receptors have been shown to affect ethanol consumption when infused directly into the ventral tegmental area (VTA) of rats. However, administration of MOR-selective antagonists into the VTA has yielded mixed results. We used RNA interference (RNAi) to specifically decrease levels of MOR messenger RNA in the VTA of mice and examined the effect on ethanol consumption in a two-bottle choice paradigm. Mice were injected in the VTA with lentivirus expressing either a small hairpin RNA (shRNA) targeting MOR or a control shRNA. One week after virus injection, mice were examined for ethanol consumption in a two-bottle choice experiment with increasing concentrations of ethanol over the course of 1 month. Expression of an shRNA targeting MOR in the VTA led to a significant reduction in ethanol consumption. These results strengthen the hypothesis that MOR in the VTA is one of the key brain substrates mediating alcohol consumption. The RNAi combined with lentiviral delivery can be used successfully in brain to effect a sustained reduction in expression of specific genes for behavioral analysis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 728-735 |
| Number of pages | 8 |
| Journal | Genes, Brain and Behavior |
| Volume | 6 |
| Issue number | 8 |
| DOIs | |
| State | Published - Nov 1 2007 |
| Externally published | Yes |
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Keywords
- Ethanol consumption
- Lentivirus
- Opioid receptor
- RNA interference
- Ventral tegmental area
ASJC Scopus subject areas
- Genetics
- Neurology
- Behavioral Neuroscience
Cite this
Downregulation of mu opioid receptor by RNA interference in the ventral tegmental area reduces ethanol consumption in mice. / Lasek, A. W.; Janak, P. H.; He, L.; Whistler, Jennifer; Heberlein, U.
In: Genes, Brain and Behavior, Vol. 6, No. 8, 01.11.2007, p. 728-735.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Downregulation of mu opioid receptor by RNA interference in the ventral tegmental area reduces ethanol consumption in mice
AU - Lasek, A. W.
AU - Janak, P. H.
AU - He, L.
AU - Whistler, Jennifer
AU - Heberlein, U.
PY - 2007/11/1
Y1 - 2007/11/1
N2 - Pharmacological and genetic studies have implicated the mu opioid receptor (MOR) in the regulation of ethanol intake in animal models and humans. Non-specific antagonists of opioid receptors have been shown to affect ethanol consumption when infused directly into the ventral tegmental area (VTA) of rats. However, administration of MOR-selective antagonists into the VTA has yielded mixed results. We used RNA interference (RNAi) to specifically decrease levels of MOR messenger RNA in the VTA of mice and examined the effect on ethanol consumption in a two-bottle choice paradigm. Mice were injected in the VTA with lentivirus expressing either a small hairpin RNA (shRNA) targeting MOR or a control shRNA. One week after virus injection, mice were examined for ethanol consumption in a two-bottle choice experiment with increasing concentrations of ethanol over the course of 1 month. Expression of an shRNA targeting MOR in the VTA led to a significant reduction in ethanol consumption. These results strengthen the hypothesis that MOR in the VTA is one of the key brain substrates mediating alcohol consumption. The RNAi combined with lentiviral delivery can be used successfully in brain to effect a sustained reduction in expression of specific genes for behavioral analysis.
AB - Pharmacological and genetic studies have implicated the mu opioid receptor (MOR) in the regulation of ethanol intake in animal models and humans. Non-specific antagonists of opioid receptors have been shown to affect ethanol consumption when infused directly into the ventral tegmental area (VTA) of rats. However, administration of MOR-selective antagonists into the VTA has yielded mixed results. We used RNA interference (RNAi) to specifically decrease levels of MOR messenger RNA in the VTA of mice and examined the effect on ethanol consumption in a two-bottle choice paradigm. Mice were injected in the VTA with lentivirus expressing either a small hairpin RNA (shRNA) targeting MOR or a control shRNA. One week after virus injection, mice were examined for ethanol consumption in a two-bottle choice experiment with increasing concentrations of ethanol over the course of 1 month. Expression of an shRNA targeting MOR in the VTA led to a significant reduction in ethanol consumption. These results strengthen the hypothesis that MOR in the VTA is one of the key brain substrates mediating alcohol consumption. The RNAi combined with lentiviral delivery can be used successfully in brain to effect a sustained reduction in expression of specific genes for behavioral analysis.
KW - Ethanol consumption
KW - Lentivirus
KW - Opioid receptor
KW - RNA interference
KW - Ventral tegmental area
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UR - http://www.scopus.com/inward/citedby.url?scp=35748931731&partnerID=8YFLogxK
U2 - 10.1111/j.1601-183X.2007.00303.x
DO - 10.1111/j.1601-183X.2007.00303.x
M3 - Article
C2 - 17428267
AN - SCOPUS:35748931731
VL - 6
SP - 728
EP - 735
JO - Genes, Brain and Behavior
JF - Genes, Brain and Behavior
SN - 1601-1848
IS - 8
ER -