Relationships Among Ventral Striatal Dopamine Release, Cortisol Secretion, and Subjective Responses to Amphetamine

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 30; no. 4; pp. 821 - 832
• Main Authors: OSWALD, Lynn M, WONG, Dean F, MCCAUL, Mary, YUN ZHOU, KUWABARA, Hiroto, CHOI, Leena, BRASIC, James, WAND, Gary S
• Format: Journal Article
• Language: English
• Published: New York, NY Nature Publishing 01-04-2005; Nature Publishing Group
• Subjects: Adolescent; Adult; Affect - drug effects; Affect - physiology; Amphetamine - pharmacology; Amphetamine-Related Disorders - diagnostic imaging; Amphetamine-Related Disorders - metabolism; Amphetamine-Related Disorders - physiopathology; Biological and medical sciences; Carbon Radioisotopes; Causality; Dopamine - metabolism; Dopamine Antagonists - metabolism; Female; Functional Laterality - drug effects; Functional Laterality - physiology; Growth Hormone - blood; Humans; Hydrocortisone - blood; Hydrocortisone - secretion; Hypothalamo-Hypophyseal System - drug effects; Hypothalamo-Hypophyseal System - metabolism; Hypothalamo-Hypophyseal System - physiopathology; Male; Medical sciences; Neostriatum - drug effects; Neostriatum - metabolism; Neostriatum - physiopathology; Neuropharmacology; Pharmacology. Drug treatments; Positron-Emission Tomography; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Raclopride - metabolism; Raclopride - pharmacokinetics; Reward; Stress, Physiological - metabolism; Stress, Physiological - physiopathology; Amphetamine derivatives; Psychotropic; positron emission tomography (PET); Central nervous system; Hydrocortisone; Glucocorticoid; Encephalon; Reinforcement; Amfetamine; Release; Human; Corticosteroid; Dopamine; CNS stimulant; Steroid hormone; Secretion; Antiinflammatory agent; amphetamine; Basal ganglion; Corpus striatum; Catecholamine; cortisol; Adrenal hormone; Neurotransmitter; Emission tomography
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/sj.npp.1300667

There is evidence that stress and glucocorticoids alter drug self-administration and mesolimbic dopamine (DA) activity in preclinical models. The primary purpose of this study was to test the hypothesis that glucocorticoids are associated with psychostimulant reinforcement and DA release in humans. In total, 16 healthy adults, ages 18-27 years, underwent two consecutive 90-min PET studies with high specific activity [11C]raclopride. The first scan was preceded by intravenous saline, and the second by intravenous amphetamine (AMPH 0.3 mg/kg). DA release was defined as the percent change in raclopride binding between the placebo and AMPH scans. Measures of subjective drug effects, plasma cortisol, and growth hormone (GH) were obtained. Findings showed that cortisol levels were positively associated with AMPH-induced DA release in the left ventral striatum (LVS) and the dorsal putamen. Subjects with higher cortisol responses to AMPH also reported more positive subjective drug effects than subjects with lower cortisol responses; no association was observed between cortisol levels and negative drug effects. Higher ratings of positive drug effects were also associated with greater DA release in the LVS, dorsal putamen, and dorsal caudate. A general lack of relationship was observed between GH responses to AMPH and DA release or subjective drug responses. Our findings provide evidence of interrelationships between glucocorticoid levels, subjective responses to IV AMPH, and brain DA release in humans. The results are consistent with those of preclinical studies, suggesting that individual differences in HPA axis function may influence vulnerability to alcohol and drug dependence in humans.