Rewarding effects of opiates are absent in mice lacking the receptor for substance P

Modulation of substance P activity offers a radical new approach to the management of depression, anxiety and stress. The substance P receptor is highly expressed in areas of the brain that are implicated in these behaviours, but also in other areas such as the nucleus accumbens which mediate the mo...

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Bibliographic Details
Published in:Nature (London) 2000-05, Vol.405 (6783), p.180-183
Main Authors: Hunt, Stephen P, Murtra, Patricia, Sheasby, Anne M, De Felipe, Carmen
Format: Article
Language:English
Subjects:
Animals
Anxiety
Biological and medical sciences
Cocaine - pharmacology
Conditioning, Classical
Corpus Striatum - drug effects
Corpus Striatum - metabolism
Cyclic AMP - metabolism
Drug abuse
Drug addictions
Female
Locomotion - drug effects
Male
Medical sciences
Mental depression
Mice
Mice, Inbred C57BL
Mice, Knockout
Morphine - metabolism
Morphine - pharmacology
Morphine Dependence - metabolism
Narcotics
Narcotics - metabolism
Narcotics - pharmacology
Proto-Oncogene Proteins c-fos - biosynthesis
Receptors, Dopamine D1 - metabolism
Receptors, Dopamine D2 - metabolism
Receptors, Neurokinin-1 - deficiency
Receptors, Neurokinin-1 - genetics
Receptors, Neurokinin-1 - metabolism
Receptors, Opioid, mu - metabolism
Reward
Rodents
Toxicology
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Summary:Modulation of substance P activity offers a radical new approach to the management of depression, anxiety and stress. The substance P receptor is highly expressed in areas of the brain that are implicated in these behaviours, but also in other areas such as the nucleus accumbens which mediate the motivational properties of both natural rewards such as food and of drugs of abuse such as opiates. Here we show a loss of the rewarding properties of morphine in mice with a genetic disruption of the substance P receptor. The loss was specific to morphine, as both groups of mice responded when cocaine or food were used as rewards. The physical response to opiate withdrawal was also reduced in substance P receptor knockout mice. We conclude that substance P has an important and specific role in mediating the motivational aspects of opiates and may represent a new pharmacological route for the control of drug abuse.
ISSN:0028-0836
1476-4687
DOI:10.1038/35012069