1. ¹Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
2. ²Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
3. ³Department of Family and Community Health, University of Maryland School of Nursing, Baltimore, MD, USA
4. ⁴Russell H Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
5. ⁵Johns Hopkins Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD, USA

Correspondence: Dr GS Wand, Department of Medicine, The Johns Hopkins University School of Medicine, 720 Rutland Ave., Ross Building, Room 863, Baltimore, MD 21205, USA, Tel: +1 410 955 7225; Fax: +1 410 955 0841; E-mail: gwand@jhmi.edu

Received 13 November 2006; Revised 19 December 2006; Accepted 17 January 2007; Published online 7 March 2007.

Abstract

Preclinical studies have shown that stress and glucocorticoids increase mesolimbic dopamine (DA) and thereby facilitate psychostimulant self-administration. The relationship between stress-induced cortisol and mesolimbic DA responses to psychostimulants has not been studied in humans. To test the hypotheses that glucocorticoid responses to psychological stress are correlated with DA and subjective responses to psychostimulants in humans, 25 healthy adults (18–29 years) completed the Trier Social Stress Test (TSST) and two positron emission tomography (PET) scans with high-specific [¹¹C]raclopride. The first scan was preceded by intravenous saline and the second by amphetamine (AMPH). Findings showed that stress-induced cortisol levels were positively associated with AMPH-induced DA release in the ventral striatum and other striatal regions. Subjects with higher cortisol responses to stress also reported more positive subjective drug effects with AMPH than subjects with lower responses. The results are consistent with preclinical findings showing an interrelationship between glucocorticoids and mesolimbic DA dynamics, which may influence psychostimulant self-administration in humans.