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

Abstract

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 [11 C]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.

Enhanced Sensitivity to Stress and Drug/Alcohol Craving in Abstinent Cocaine-Dependent Individuals Compared to Social Drinkers

“…It is also interesting to note that alcohol cue-induced craving was only significantly associated with increases in anxiety rather than negative emotions, in social drinkers. This combination of both jitteriness and relaxed mood possibly representative of a hedonic arousal state following cue exposure, is consistent with previous research indicating that stress markers may mediate the rewarding properties of drugs (Oswald et al, 2005;Mendelson et al, 2005). Importantly, however, the emotional response to alcohol cues in the social drinkers was markedly different from the range of negative emotions reported following cue exposure in the cocaine participants.…”

Association of Amphetamine-Induced Striatal Dopamine Release and Cortisol Responses to Psychological Stress

“…We previously demonstrated during PET imaging in humans that AMPH-induced DA release is correlated with AMPH-induced cortisol secretion as well as with positive subjective drug responses including drug 'liking,' 'desire,' 'good effect,' 'high,' and 'rush' (Oswald et al, 2005). However, the prior study did not clarify whether cortisol responses to a psychological stressor would also be associated with DA responses to AMPH.…”

“…All participants provided written informed consent under the oversight of The Johns Hopkins School of Medicine Institutional Review Board. Sixteen of the subjects were included in our first PET study that examined the relationship between AMPH-induced cortisol vs AMPH-induced DA release (Oswald et al, 2005). Subject assessment included a medical history and physical exam performed by a physician, complete blood count, comprehensive metabolic panel (including renal and hepatic function tests), electrocardiogram, urinalysis, alcohol breathalyzer test, and urine toxicology screen.…”

“…Specifically, PET imaging has demonstrated that amphetamine (AMPH), methylphenidate, and cocaine increase mesolimbic DA concentrations and that the magnitude of DA responsiveness to these drugs of abuse correlates with their positive subjective effects (Oswald et al, 2005;Volkow et al, 2004;Martinez et al, 2004;Leyton et al, 2002). Given that the mesolimbic system is an important mediator of drug reward, it is important to understand the environmental and genetic factors that modulate its function.…”

Human Methamphetamine Pharmacokinetics Simulated in the Rat: Single Daily Intravenous Administration Reveals Elements of Sensitization and Tolerance

“…Controlled studies in humans have shown that acute administration of low AMPH doses produces subjective effects like euphoria, 'mind racing', and alertness Angrist, 1987;McTavish et al, 1999;Vollm et al, 2004); physiological changes in heart rate and blood pressure have also been monitored (Griffith and Gunne, 1977;Brown et al, 1978;Angrist et al, 1987;Angrist, 1987;Cook et al, 1993;Oswald et al, 2005). In many of these studies, when the time course of these stimulant-induced alterations was determined, a dissociation between these effects and measured or inferred plasma levels was apparent and often referred to as acute tolerance or tachyphylaxis Angrist, 1987;Cook et al, 1993;Swanson et al, 2002;Greenhill et al, 2003;Foltin and Haney, 2004).…”