Limits...
The influence of stress on the transition from drug use to addiction.

Wand G - Alcohol Res Health (2008)

Bottom Line: In turn, certain stress hormones (i.e., glucocorticoids and corticotrophin-releasing factor) also act on the brain system that mediates the rewarding experiences associated with AOD use (i.e., the mesocorticolimbic dopamine system).During the final stage of addiction, when the addicted person experiences withdrawal symptoms if no drug is consumed, chronic AOD use results in gross impairment of the normal stress response and other signaling mechanisms in the brain, resulting in a state of anxiety and internal stress.At this stage, people continue to use AODs mainly to relieve this negative-affect state.

View Article: PubMed Central - PubMed

Affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.

ABSTRACT
Stress--that is, any type of stimulus that challenges the organism's normal internal balance--induces a physiologic response involving a variety of hormones and other signaling molecules that act on, among other organs, the brain. This stress response also can influence the progression of alcohol and other drug (AOD) addiction through various stages. For example, AODs can directly activate the stress response. In turn, certain stress hormones (i.e., glucocorticoids and corticotrophin-releasing factor) also act on the brain system that mediates the rewarding experiences associated with AOD use (i.e., the mesocorticolimbic dopamine system). Moreover, elevated glucocorticoid levels and stress increase AOD self-administration in certain animal models. During a later stage of the addiction process, in contrast, excessive and/or prolonged stress may impair the reward system, inducing heavier AOD use to maintain the rewarding experience. During the final stage of addiction, when the addicted person experiences withdrawal symptoms if no drug is consumed, chronic AOD use results in gross impairment of the normal stress response and other signaling mechanisms in the brain, resulting in a state of anxiety and internal stress. At this stage, people continue to use AODs mainly to relieve this negative-affect state.

Show MeSH

Related in: MedlinePlus

Regulation of the mesocorticolimbic dopamine system. Cell bodies of dopamine-releasing (i.e., dopaminergic) neurons located in the ventral tegmental area (VTA) are activated by glutamate-releasing neurons. This activation leads to the release of dopamine in the nucleus accumbens (NAc), resulting in the activation of other neurons whose cell bodies are located in the NAc and in the generation of rewarding and reinforcing experiences. Alcohol and other drugs (AODs), corticotrophin-releasing factor (CRF), and stress and stress-induced hormones (i.e., glucocorticoids) all can influence this chain of events by acting on the glutamate-releasing neurons, dopaminergic neurons in the VTA, or dopamine release in the NAc.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3860459&req=5

f3-arh-31-2-119: Regulation of the mesocorticolimbic dopamine system. Cell bodies of dopamine-releasing (i.e., dopaminergic) neurons located in the ventral tegmental area (VTA) are activated by glutamate-releasing neurons. This activation leads to the release of dopamine in the nucleus accumbens (NAc), resulting in the activation of other neurons whose cell bodies are located in the NAc and in the generation of rewarding and reinforcing experiences. Alcohol and other drugs (AODs), corticotrophin-releasing factor (CRF), and stress and stress-induced hormones (i.e., glucocorticoids) all can influence this chain of events by acting on the glutamate-releasing neurons, dopaminergic neurons in the VTA, or dopamine release in the NAc.

Mentions: As mentioned earlier, the ultimate result of the body’s stress response via the HPA axis is the release of glucocorticoids from the adrenal glands. Therefore, to investigate if and how stress can influence the perceived effects of AODs, one approach is to study, in laboratory animals, how glucocorticoids alter mesocorticolimbic signaling and thereby modulate (e.g., amplify) the positive reinforcing effects of AODs. For example, researchers lowered animals’ glucocorticoid concentrations in the blood by removing the animals’ adrenal glands (i.e., performing an adrenalectomy). This manipulation led to reduced dopamine levels in the NAc, both when the VTA neurons were in a resting state and when they were stimulated (Barrot et al. 2000; Piazza et al. 1996) (see figure 3). When the animals were injected with corticosterone to replace adrenal glucocorticoid production, normal dopamine levels were restored. Additional analyses demonstrated that the effects of adrenalectomy on dopamine levels were limited only to certain regions of the NAc (i.e., the shell of the NAc) (Barrot et al. 2000). Furthermore, corticosterone’s effects on dopamine concentrations in the shell of the NAc involve activation of the glucocorticoid (type II) receptors, which only are activated at higher corticosterone concentrations but not the mineralocorticoid (type I) receptors, which also are activated at lower corticosterone concentrations (Marinelli and Piazza 2002).


The influence of stress on the transition from drug use to addiction.

Wand G - Alcohol Res Health (2008)

Regulation of the mesocorticolimbic dopamine system. Cell bodies of dopamine-releasing (i.e., dopaminergic) neurons located in the ventral tegmental area (VTA) are activated by glutamate-releasing neurons. This activation leads to the release of dopamine in the nucleus accumbens (NAc), resulting in the activation of other neurons whose cell bodies are located in the NAc and in the generation of rewarding and reinforcing experiences. Alcohol and other drugs (AODs), corticotrophin-releasing factor (CRF), and stress and stress-induced hormones (i.e., glucocorticoids) all can influence this chain of events by acting on the glutamate-releasing neurons, dopaminergic neurons in the VTA, or dopamine release in the NAc.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860459&req=5

f3-arh-31-2-119: Regulation of the mesocorticolimbic dopamine system. Cell bodies of dopamine-releasing (i.e., dopaminergic) neurons located in the ventral tegmental area (VTA) are activated by glutamate-releasing neurons. This activation leads to the release of dopamine in the nucleus accumbens (NAc), resulting in the activation of other neurons whose cell bodies are located in the NAc and in the generation of rewarding and reinforcing experiences. Alcohol and other drugs (AODs), corticotrophin-releasing factor (CRF), and stress and stress-induced hormones (i.e., glucocorticoids) all can influence this chain of events by acting on the glutamate-releasing neurons, dopaminergic neurons in the VTA, or dopamine release in the NAc.
Mentions: As mentioned earlier, the ultimate result of the body’s stress response via the HPA axis is the release of glucocorticoids from the adrenal glands. Therefore, to investigate if and how stress can influence the perceived effects of AODs, one approach is to study, in laboratory animals, how glucocorticoids alter mesocorticolimbic signaling and thereby modulate (e.g., amplify) the positive reinforcing effects of AODs. For example, researchers lowered animals’ glucocorticoid concentrations in the blood by removing the animals’ adrenal glands (i.e., performing an adrenalectomy). This manipulation led to reduced dopamine levels in the NAc, both when the VTA neurons were in a resting state and when they were stimulated (Barrot et al. 2000; Piazza et al. 1996) (see figure 3). When the animals were injected with corticosterone to replace adrenal glucocorticoid production, normal dopamine levels were restored. Additional analyses demonstrated that the effects of adrenalectomy on dopamine levels were limited only to certain regions of the NAc (i.e., the shell of the NAc) (Barrot et al. 2000). Furthermore, corticosterone’s effects on dopamine concentrations in the shell of the NAc involve activation of the glucocorticoid (type II) receptors, which only are activated at higher corticosterone concentrations but not the mineralocorticoid (type I) receptors, which also are activated at lower corticosterone concentrations (Marinelli and Piazza 2002).

Bottom Line: In turn, certain stress hormones (i.e., glucocorticoids and corticotrophin-releasing factor) also act on the brain system that mediates the rewarding experiences associated with AOD use (i.e., the mesocorticolimbic dopamine system).During the final stage of addiction, when the addicted person experiences withdrawal symptoms if no drug is consumed, chronic AOD use results in gross impairment of the normal stress response and other signaling mechanisms in the brain, resulting in a state of anxiety and internal stress.At this stage, people continue to use AODs mainly to relieve this negative-affect state.

View Article: PubMed Central - PubMed

Affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.

ABSTRACT
Stress--that is, any type of stimulus that challenges the organism's normal internal balance--induces a physiologic response involving a variety of hormones and other signaling molecules that act on, among other organs, the brain. This stress response also can influence the progression of alcohol and other drug (AOD) addiction through various stages. For example, AODs can directly activate the stress response. In turn, certain stress hormones (i.e., glucocorticoids and corticotrophin-releasing factor) also act on the brain system that mediates the rewarding experiences associated with AOD use (i.e., the mesocorticolimbic dopamine system). Moreover, elevated glucocorticoid levels and stress increase AOD self-administration in certain animal models. During a later stage of the addiction process, in contrast, excessive and/or prolonged stress may impair the reward system, inducing heavier AOD use to maintain the rewarding experience. During the final stage of addiction, when the addicted person experiences withdrawal symptoms if no drug is consumed, chronic AOD use results in gross impairment of the normal stress response and other signaling mechanisms in the brain, resulting in a state of anxiety and internal stress. At this stage, people continue to use AODs mainly to relieve this negative-affect state.

Show MeSH
Related in: MedlinePlus