Fear and anxiety: relationship to noradrenergic function.

The experiences of human fear and anxiety are discussed within the context of locus ceruleus function in animals. The rationale for studying correlates of noradrenergic function, such as 3-methoxy-4-hydroxyphenethylene glycol (MHPG), is reviewed, and data demonstrating a positive correlation between plasma free MHPG and state anxiety in normal volunteers is presented. The behavioral effects of oral caffeine (240-720 mg), intravenous clonidine (2 micrograms/kg), and oral yohimbine (20 mg) were studied in various psychiatric patients and normal volunteers. Caffeine and yohimbine had anxiogenic properties; conversely, clonidine reduced self-rated measures of anxiety across a wide spectrum of psychiatric conditions. These findings expand previous research indicating that noradrenergic hyperactivity may be associated with many types of human fear and anxiety.