Substance P (SP) is the most widely distributed neuropeptide in central nervous system (CNS) where it participates in numerous physiological and pathophysiological processes including stress and anxiety related behaviors.
Although alcohol use disorder and anxiety disorders are highly comorbid in humans, controversy remains regarding whether anxiety predisposes individuals to alcohol reward, and the relationship with neurokinin-1 receptor (NK1R) is unclear.
Alterations in the SP-NK1 system have also been observed in human anxiety disorders, yet little is known about the relation between this system and individual differences in personality traits associated with anxiety propensity and approach-avoidance behavior, including trait anxiety, neuroticism, and extraversion.
The identification of Dex/forskolin response elements in the TAC1 promoter in amygdala neurones suggests a possible link in the chain of molecular events connecting GR activation and anxiety.
PDE10A, TAC1 and other genes uncovered by our work provide a molecular basis for the frequently observed clinical co-morbidity and interdependence between anxiety and other major psychiatric disorders, and suggest schizo-anxiety as a possible new nosological domain.
Increasing evidence suggests that substance P (SP) neurokinin-1 (NK1) receptors are involved in stress and emotional responses, representing a potential target for the treatment of anxiety and depression in humans.
This review summarizes the pre-clinical evidence derived from pharmacological and transgenic animal studies that suggests an important role for the substance P/neurokinin 1 system in anxiety and depression.