Stress can trigger drug-seeking, increase self-administration rates, and enhance drug reward. A number of stress-related neuropeptides have been shown to mediate these behavioral processes. The most studied peptide in this category is corticotropin releasing hormone (CRH), which has been shown to mediate stress-induced reinstatement of drug seeking, escalated self-administration, and drug withdrawal, but does not seem to be involved in baseline drug self-administration or cue-induced reinstatement. This pattern of effects holds for many classes of drugs including alcohol, opiates, and psychostimulants. The neurokinin-1 receptor (NK1R) is the preferred receptor for the endogenous stress-related neuropeptide substance P (SP). The SP/NK1R system is a major mediator of stress and anxiety, and over the last several years it has been demonstrated that the SP/NK1R system can have effects similar to CRH on drug taking and drug seeking. Specifically, NK1R inhibition has been shown to attenuate escalated self-administration of alcohol and stress-induced reinstatement of alcohol and cocaine seeking. However, in contrast to other stress systems, the NK1R also appears to have a role in primary reward and reinforcement for opiates. Here, we outline the role of NK1R in drug seeking behaviors, and highlight recent results from clinical studies that suggest that the NK1R may be a promising drug target going forward.
- The American Society for Pharmacology and Experimental Therapeutics