Cortisol secretion patterns in addiction and addiction risk

Abstract

Addiction to alcohol or nicotine involves altered functioning of the brain's motivational systems. Altered functioning of the hypothalamic-pituitary-adrenocortical (HPA) axis may hold clues to the nature of the motivational changes accompanying addiction and vulnerability to addiction. Alcohol and nicotine show at least three forms of interaction with HPA functioning. Acute intake of both substances causes stress-like cortisol responses. Their persistent use may dysregulate the HPA. Finally, the risk for dependence and for relapse after quitting may be associated with deficient cortisol reactivity to a variety of stressors. The HPA is regulated at the hypothalamus by diurnal and metabolic signals, but during acute emotional states, its regulation is superseded by signals from the limbic system and prefrontal cortex. This top-down organization makes the HPA responsive to inputs that reflect motivational processes. The HPA is accordingly a useful system for studying psychophysiological reactivity in persons who may vary in cognitive, emotional, and behavioral tendencies associated with addiction and risk for addiction. Chronic, heavy intake of alcohol and nicotine may cause modifications in these frontal-limbic interactions and may account for HPA response differences in seen in alcoholics and smokers. In addition, preexisting alterations in frontal-limbic interactions with the HPA may reflect addiction-proneness, as shown in studies of offspring of alcohol- and drug-abusing parents. Continuing research on the relationship between HPA function, stress responsivity, and the addictions may yield insights into how the brain's motivational systems support addictions and risk for addictions.

Fig. 1

The 24-h plasma cortisol secretion curve in humans. The secretion peak occurs near the time of awakening and has a nadir during the first half of the sleep cycle. Minor rises can be seen in relation to meals at midday and early evening.

Fig. 2

Effects of opioid blockade on cortisol secretion. Opioid blockade acts in the brain to increase cortisol secretion and alter mood. (1) Opioid neurons from the arcuate nucleus of the hypothalamus normally inhibit CRF output by neurons of the PVN, reducing CRF secretion at the pituitary gland and thereby reducing ACTH release and cortisol production. Opioid blockade releases the PVN from this inhibitory influence, allowing cortisol production to increase. (2) The locus ceruleus contains about 85% of the NE cell bodies in the central nervous system, and it is largely responsible for the amount of global activation in the brain. Opioid neurons in the brainstem normally inhibit the NE-producing cells of the locus ceruleus. Opioid blockade releases the locus ceruleus from this inhibitory influence, allowing NE to activate the CRF-neurons of the PVN, resulting in increased cortisol production. (3) The nucleus accumbens is a site of DA release in response to all drugs of abuse. This nucleus is in extensive two-way communication with the prefrontal cortex. Opioid neurons from the arcuate nucleus normally activate DA release at the nucleus accumbens. Opioid blockade inhibits this effect, reducing DA release by the nucleus accumbens at the prefrontal cortex. This may alter hedonic states and attention to reward cues. Cortisol feedback to the central nervous system is capable of altering the excitability of dopamine neurons as discussed in the text. ACTH=adrenocorticotropic hormone; CNS=central nervous system; CRF=corticotropin releasing factor; DA=dopamine; LC=locus ceruleus; NE=norepinephrine; VTA=ventral tegmental area. Adapted with permission of the author (Wand et al., 1998).