HPA axis and stimulant dependence: an enigmatic relationship.

Clinical and preclinical evidence links stress to drug dependence. Stress is accompanied by the rapid modification of brain and body physiology which leads to release of neuroactive hormones, including biogenic amines and adrenal steroids, which activate the same brain circuitry, as stimulant drugs, such as cocaine and amphetamines. Some preclinical studies showed that stress and elevated plasma concentrations of glucocorticoids increase acquisition and maintenance of stimulant use in rats, whereas other studies revealed that animals with inherently hypoactive HPA axis are more vulnerable to stimulant "abuse". In humans cocaine acutely activates the HPA axis, and in chronic cocaine abusers early abstinence is accompanied by alterations of the HPA axis function, with distinct patterns of hormonal changes characteristic for different subgroups of addicts. Some of these changes correspond to psychiatric comorbidities, which may be predictive of propensity to relapse. Hemispheric laterality plays a role in the stress-induced activation of the HPA axis, with right prefrontal cortex (PFC) having mostly stimulatory effects and the left, inhibitory effects. Brain-imaging studies showed preferential alteration of structure and function of the right cerebral hemisphere in cocaine addicts. Activation of the right PFC and inhibition of the left was noted in typical depressive disorders, and right hemispheric hypoactivity was reported in attention deficit hyperactivity and antisocial personality disorders, which are highly comorbid with stimulant dependence. Distinct patterns of hemispheric predominance or hypofunction between individuals may contribute to vulnerability or resilience to stimulant dependence. The nature and significance of the link between stress and activity of HPA axis, and vulnerability to drug dependence is not clear and deserves further study.