Neurokinin 1 Receptor Antagonism as a Possible Therapy for Alcoholism

  title={Neurokinin 1 Receptor Antagonism as a Possible Therapy for Alcoholism},
  author={David Ted George and Jodi M. Gilman and Jacqueline Hersh and Annika Thorsell and David Herion and Christopher Geyer and Xiaomei Peng and William Kielbasa and Robert R. Rawlings and John E Brandt and Donald R. Gehlert and Johannes T. Tauscher and Stephen P Hunt and Daniel W. Hommer and Markus Heilig},
  pages={1536 - 1539}
Alcohol dependence is a major public health challenge in need of new treatments. As alcoholism evolves, stress systems in the brain play an increasing role in motivating continued alcohol use and relapse. We investigated the role of the neurokinin 1 receptor (NK1R), a mediator of behavioral stress responses, in alcohol dependence and treatment. In preclinical studies, mice genetically deficient in NK1R showed a marked decrease in voluntary alcohol consumption and had an increased sensitivity to… 

Disentangling the Genetics of Alcoholism : Understanding Pathophysiology and Improving Treatment 2010 The NK 1 antagonist L 822429 inhibits stress-induced reinstatement of alcohol seeking behavior in rats

The results indicate NK1 antagonists generally, and L822429 specifically, as promising candidates for pharmacotherapy for alcoholism.

The NK1 antagonist L822429 inhibits stress-induced reinstatement of alcohol seeking behavior in rats

The results indicate NK1 antagonists generally, and L822429 specifically, as promising candidates for pharmacotherapy for alcoholism.

Alcohol dependence potentiates substance P/neurokinin-1 receptor signaling in the rat central nucleus of amygdala

Examination of regulation of GABA transmission in the medial subdivision of the central amygdala (CeM) by the SP/NK-1R system, and its neuroadaptation following chronic alcohol exposure confirms that NK-1Rs are promising targets for the treatment of alcohol use disorder.

Neurobiology of Alcohol Dependence: Focus on Motivational Mechanisms

Recent research focusing on brain arousal, reward, and stress systems is accelerating the understanding of the components of alcohol dependence and contributing to the development of new treatment strategies.

Neurokinin receptors in drug and alcohol addiction

  • J. Schank
  • Biology, Psychology
    Brain Research
  • 2020

Medication treatment of different types of alcoholism.

  • B. Johnson
  • Psychology, Medicine
    The American journal of psychiatry
  • 2010
Although preliminary work on the pharmacogenetics of alcoholism and its treatment has been promising, the assignment to treatment still depends on clinical assessment and brief behavioral interventions that encourage the patient to set goals for a reduction in heavy drinking or abstinence also are part of optimal therapy.



Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamo–pituitary–adrenocortical axis

The hypothesis that naltrexone reduces desire to drink and the amount of alcohol consumed in alcohol-dependent subjects is confirmed, and this effect may be related in part to nALTrexone's ability to activate the hypothalamo–pituitary–adrenocortical axis.

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

It is concluded 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.

Pharmacogenetic studies of alcohol self-administration and withdrawal

If a functional relationship between alcohol self-administration and withdrawal exists, severity of acute withdrawal, seen after even a single alcohol exposure, may serve as a viable behavioral marker for alcoholism risk in individuals with relatively little alcohol experience.

Imaging stress- and cue-induced drug and alcohol craving: association with relapse and clinical implications.

Altered function in these brain regions is associated with stress-induced and drug cue-induced craving states and an increased susceptibility to relapse, and alterations can serve as markers to identify relapse propensity and a more severe course of addiction.

Additive Effect of Stress and Drug Cues on Reinstatement of Ethanol Seeking: Exacerbation by History of Dependence and Role of Concurrent Activation of Corticotropin-Releasing Factor and Opioid Mechanisms

The results document that stress and drug-related environmental stimuli interact to augment the resumption of drug seeking after extinction and suggest that this effect results from concurrent activation of opioid and CRF transmission.

Distinct mechanism for antidepressant activity by blockade of central substance P receptors.

The localization of substance P in brain regions that coordinate stress responses and receive convergent monoaminergic innervation suggested that substance P antagonists might have psychotherapeutic