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 man agement of depression, anxiety and stress(1-3). The substance P receptor is highly expressed in areas of the brain that are implicated in these behavi ours, but also in other areas such as the nucleus accumbens which mediate t he motivational properties of both natural rewards such as food and of drug s of abuse such as opiates(4-7). Here we show a loss of the rewarding prope rties of morphine in mice with a genetic disruption of the substance P rece ptor. The loss was specific to morphine, as both groups of mice responded w hen cocaine or food were used as rewards. The physical response to opiate w ithdrawal was also reduced in substance P receptor knockout mice. We conclu de that substance P has an important and specific role in mediating the mot ivational aspects of opiates and may represent a new pharmacological route for the control of drug abuse.