The hypothalamo-pituitary-adrenal (HPA) axis is involved in all aspects of cocaine self-administration. Corticosterone seems to be crucial for the acquisition of drug use since self-administration does not occur unless this stress hormone is increased above a critical reward threshold. Increasing circulating levels of corticosterone also augments sensitivity to low doses of cocaine, possibly from a sensitization-associated phenomenon involving dopamine, suggesting that exposure to stress can increase individual vulnerability to cocaine. Drugs affecting the synthesis and/or secretion of corticosterone decrease ongoing, low-dose cocaine self-administration. When higher doses falling on the descending limb of the cocaine dose-response curve are self-administered, plasma corticosterone can still reach this reward threshold even when synthesis is inhibited and drug intake is not affected. Corticotropin-releasing hormone (CRH) seems to play a more prominent role in the maintenance of cocaine self-administration and may even be involved in the incentive motivation for the drug. Corticosterone and CRH are also critical for the stress-and cue-induced reinstatement of extinguished cocaine-seeking behavior. Therefore, cocaine self-administration may represent an attempt to seek out specific sensations, with the internal state produced being very similar to that perceived by individuals who engage in risky, thrill-seeking behavior. During abstinence, exposure to stressors or cocaine-associated cues can stimulate the HPA axis to remind the individual about the effects of cocaine, thus producing craving and promoting relapse. Stress reduction, either alone or in combination with pharmacotherapies targeting the HPA axis may prove beneficial in reducing cravings and promoting abstinence in individuals seeking treatment for cocaine addiction.The role of stress and the subsequent activation of the hypothalamo-pituitary-adrenal (HPA) axis in drug addiction has been under investigation in a number of laboratories for several years now. Subsequently, a number of excellent review articles have recently been published in an attempt to summarize the relevant research findings and to provide a rational explanation for these data

Neuronal systems involved in the initiation of cocaine reinforcement were investigated by identifying brain sites where direct application of the drug was reinforcing. This was accomplished by allowing rats to self-administer picomolar concentrations of cocaine into discrete brain regions. The medial prefrontal cortex supported self-administration, while the nucleus accumbens and ventral tegmental area did not. Self-administration could be attenuated by including equimolar concentrations of the dopaminergic D2-receptor antagonist sulpiride in the microinjection system. These results imply that cocaine reinforcement is mediated in part through a direct action on mesocortical dopaminergic receptors.

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While the opioid epidemic has garnered significant attention, the use of methamphetamines is growing worldwide independent of wealth or region. Following overdose and accidents, the leading cause of death in methamphetamine users is cardiovascular disease, because of significant effects of methamphetamine on vasoconstriction, pulmonary hypertension, atherosclerotic plaque formation, cardiac arrhythmias, and cardiomyopathy. In this review, we examine the current literature on methamphetamine-induced changes in cardiovascular health, discuss the potential mechanisms regulating these varied effects, and highlight our deficiencies in understanding how to treat methamphetamine-associated cardiovascular dysfunction.