Elsevier

Physiology & Behavior

Volume 106, Issue 1, 12 April 2012, Pages 58-64
Physiology & Behavior

Allostasis and addiction: Role of the dopamine and corticotropin-releasing factor systems

https://doi.org/10.1016/j.physbeh.2011.11.004Get rights and content

Abstract

Allostasis, originally conceptualized to explain persistent morbidity of arousal and autonomic function, is defined as the process of achieving stability through physiological or behavioral change. Two types of biological processes have been proposed to describe the mechanisms underlying allostasis in drug addiction, a within-system adaptation and a between-system adaptation. In the within-system process, the drug elicits an opposing, neutralizing reaction within the same system in which the drug elicits its primary and unconditioned reinforcing actions, while in the between-system process, different neurobiological systems that the one initially activated by the drug are recruited. In this review, we will focus our interest on alterations in the dopaminergic and corticotropin releasing factor systems as within-system and between-system neuroadaptations respectively, that underlie the opponent process to drugs of abuse. We hypothesize that repeated compromised activity in the dopaminergic system and sustained activation of the CRF–CRF1R system with withdrawal episodes may lead to an allostatic load contributing significantly to the transition to drug addiction.

Highlights

► The opponent process theory postulates that drugs trigger two opposing motivational process. ► The a-process has fast onset and offset and the b-process is opposite, slower to start and last longer. ► Decreased dopaminergic function in the NAC and CeA mediate the habituation of the a-process. ► Activation of the CRF systems in the CeA and VTA mediates the increase in b-process in dependent subjects. ► Interaction between the dopamine and CRF systems may represent the opponent-process mechanisms of drug withdrawal.

Section snippets

Allostasis

Allostasis, originally conceptualized to explain persistent morbidity of arousal and autonomic function, is defined as the process of achieving stability through physiological or behavioral change [1], [2]. Allostasis involves a feed-forward mechanism rather than the negative feedback mechanisms of homeostasis, with continuous re-evaluation of need and continuous readjustment of all parameters toward new set points. Thus, the very physiological mechanism that allows rapid responses to

Drug addiction

Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take the drug, loss of control in limiting drug intake, and emergence of a negative emotional state, reflecting a motivational withdrawal syndrome, when access to the drug is prevented (defined here as dependence; [10]). Clinically, the occasional but limited use of a drug with the potential for abuse or dependence is distinct from escalated drug intake and the emergence of a chronic drug-dependent state.

Motivation, opponent process, and addiction

Motivation is a state that can be defined as a “tendency of the whole animal to produce organized activity” [17]. The concept of motivation was linked inextricably with hedonic, affective, or emotional states in addiction in the context of temporal dynamics by Solomon's opponent process theory of motivation. [18] postulated that hedonic, affective, or emotional states, once initiated, are automatically modulated by the central nervous system with mechanisms that reduce the intensity of hedonic

Role of the dopaminergic system in the motivational response that underlies the opponent process of drug abuse

The mesolimbic dopaminergic system is formed by the dopaminergic cell bodies in the ventral tegmental area (VTA) and their projections to the ventral striatum. The VTA also possesses a population of γ-aminobutyric acid (GABA) neurons that provide inhibitory inputs to dopamine cells and influence other structures, such as the pedunculopontine tegmental nucleus and glutamatergic neurons [21]. The VTA receives its main excitatory glutamatergic and cholinergic inputs from the ventromedial

Role of the corticotropin-releasing factor system in the motivational response that underlies the opponent process of drug abuse

Within the domain of changes in reward function, the primary deficit is hypothesized to be a neuroadaptational shift in how rewards are processed. More specifically, a loss of positive reinforcement and a recruitment of negative reinforcement are hypothesized to occur within a specific basal forebrain area termed the extended amygdala. The extended amygdala has been identified by neuroanatomical studies [53], [54] as a separate entity within the basal forebrain and has been hypothesized to be a

Interaction between the dopamine and corticotropin-releasing factor systems

The mesolimbic dopaminergic and extended amygdala CRF systems have long been studied independently and often viewed as mutually exclusive in the drug addiction field. However, recent work has demonstrated that these two systems can powerfully interact with each other, suggesting that dysregulation of this interaction may be lead to the development of drug dependence and relapse. Very few studies have investigated the role of dopamine in CRF release in the extended amygdala, despite the fact

Conclusions

Acute withdrawal from drugs of abuse produces opponent process-like changes in reward neurotransmitters in specific elements of reward circuitry associated with the mesolimbic dopaminergic system and recruitment of the extended amygdala and CRF stress systems that motivationally oppose the acute hedonic effects of drugs of abuse. Such changes in the dopamine and CRF these brain systems associated with the development of motivational aspects of withdrawal are hypothesized to be a major source of

Acknowledgments

This is publication number 21324 from The Scripps Research Institute. This work was supported by the National Institutes of Health grant DA04398, DA10072, DA04343, and DA023597 from the National Institute on Drug Abuse, AA08459, and AA06420 from the National Institute on Alcohol Abuse and Alcoholism, and the Pearson Center for Alcoholism and Addiction Research. The authors would like to thank Michael Arends for his help with manuscript preparation.

References (126)

  • R.A. Wise

    Brain reward circuitry: insights from unsensed incentives

    Neuron

    (2002)
  • T.E. Robinson et al.

    The neural basis of drug craving: an incentive-sensitization theory of addiction

    Brain Res Rev

    (1993)
  • C. Orsini et al.

    Dopamine partial agonist reverses amphetamine withdrawal in rats

    Neuropsychopharmacology

    (2001)
  • E.L. Gardner et al.

    Cannabinoid transmission and reward-related events

    Neurobiol Dis

    (1998)
  • F. Weiss et al.

    Basal extracellular dopamine levels in the nucleus accumbens are decreased during cocaine withdrawal after unlimited-access self-administration

    Brain Res

    (1992)
  • G.F. Alheid et al.

    New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid, and corticopetal components of substantia innominata

    Neuroscience

    (1988)
  • G.F. Koob et al.

    Neuroscience of addiction

    Neuron

    (1998)
  • Y.S. Allen et al.

    Neuropeptide Y in the stria terminalis: evidence for an amygdalofugal projection

    Brain Res

    (1984)
  • H.W. Dong et al.

    Topography of projections from amygdala to bed nuclei of the stria terminalis

    Brain Res Rev

    (2001)
  • T.S. Gray et al.

    Peptide immunoreactive neurons in the amygdala and the bed nucleus of the stria terminalis project to the midbrain central gray in the rat

    Peptides

    (1992)
  • T. Kozicz

    Axon terminals containing tyrosine hydroxylase- and dopamine-β-hydroxylase immunoreactivity form synapses with galanin immunoreactive neurons in the lateral division of the bed nucleus of the stria terminalis in the rat

    Brain Res

    (2001)
  • A. Lesur et al.

    Chemoanatomic compartments in the human bed nucleus of the stria terminalis

    Neuroscience

    (1989)
  • M.J. Nijsen et al.

    CRH signalling in the bed nucleus of the stria terminalis is involved in stress-induced cardiac vagal activation in conscious rats

    Neuropsychopharmacology

    (2001)
  • P. Pompei et al.

    Bed nucleus of the stria terminalis: site for the antinatriorexic action of tachykinins in the rat

    Pharmacol Biochem Behav

    (1991)
  • M.F. Olive et al.

    Elevated extracellular CRF levels in the bed nucleus of the stria terminalis during ethanol withdrawal and reduction by subsequent ethanol intake

    Pharmacol Biochem Behav

    (2002)
  • G.F. Koob et al.

    Corticotropin releasing factor, stress and behavior

    Semin Neurosci

    (1994)
  • S. Rassnick et al.

    Microinjection of a corticotropin-releasing factor antagonist into the central nucleus of the amygdala reverses anxiogenic-like effects of ethanol withdrawal

    Brain Res

    (1993)
  • A.W. Bruijnzeel et al.

    Corticotropin-releasing factor-1 receptor activation mediates nicotine withdrawal-induced deficit in brain reward function and stress-induced relapse

    Biol Psychiatry

    (2009)
  • N.E. Goeders et al.

    Effects of the CRH receptor antagonist CP-154,526 on intravenous cocaine self-administration in rats

    Neuropsychopharmacology

    (2000)
  • G.R. Breese et al.

    Chronic alcohol neuroadaptation and stress contribute to susceptibility for alcohol craving and relapse

    Pharmacol Ther

    (2011)
  • M. Smialowska et al.

    Effect of 6-hydroxydopamine on neuropeptide Y and corticotropin-releasing factor expression in rat amygdala

    Neuroscience

    (1999)
  • M.J. Eaton et al.

    Dopamine receptor-mediated regulation of corticotropin-releasing hormone neurons in the hypothalamic paraventricular nucleus

    Brain Res

    (1996 Oct 28)
  • W. Francesconi et al.

    Intrinsic neuronal plasticity in the juxtacapsular nucleus of the bed nuclei of the stria terminalis (jcBNST)

    Prog Neuropsychopharmacol Biol Psychiatry

    (2009)
  • D. Rodaros et al.

    Corticotropin-releasing factor projections from limbic forebrain and paraventricular nucleus of the hypothalamus to the region of the ventral tegmental area

    Neuroscience

    (2007)
  • M. Sauvage et al.

    Detection of corticotropin-releasing hormone receptor 1 immunoreactivity in cholinergic, dopaminergic and noradrenergic neurons of the murine basal forebrain and brainstem nuclei: potential implication for arousal and attention

    Neuroscience

    (2001)
  • M.A. Ungless et al.

    Corticotropin-releasing factor requires CRF binding protein to potentiate NMDA receptors via CRF receptor 2 in dopamine neurons

    Neuron

    (2003)
  • T. Muramatsu et al.

    Corticotropin-releasing factor receptor type 1, but not type 2, in the ventromedial hypothalamus modulates dopamine release in female rats

    Pharmacol Biochem Behav

    (2006)
  • Y. Kim et al.

    Regulation of somatodendritic dopamine release by corticotropin-releasing factor via the inhibition of voltage-operated Ca2 + channels

    Neurosci Lett

    (2009)
  • P. Sterling et al.

    Allostasis: a new paradigm to explain arousal pathology

  • J. Schulkin

    Social allostasis: anticipatory regulation of the internal milieu

    Front Evol Neurosci

    (2011)
  • T.E. Seeman et al.

    Exploring a new concept of cumulative biological risk: MacArthur studies of successful aging

    Proc Natl Acad Sci USA

    (2011)
  • T.E. Seeman et al.

    Price of adaptation: allostatic load and its health consequences. MacArthur studies of successful aging

    Arch Intern Med

    (1997)
  • A.T. Geronimus et al.

    “Weathering” and age patterns of allostatic load scores among blacks and whites in the United States

    Am J Public Health

    (2006)
  • G.F. Koob et al.

    Drug abuse: hedonic homeostatic dysregulation

    Science

    (1997)
  • B.S. McEwen

    Stress, adaptation, and disease: allostasis and allostatic load

  • G.W. Evans et al.

    Cumulative risk, maternal responsiveness, and allostatic load among young adolescents

    Dev Psychol

    (2007)
  • D.A. Glover et al.

    Allostatic load in women with and without PTSD symptoms

    Psychiatry

    (2006)
  • G.F. Koob et al.

    Addiction and the brain antireward system

    Annu Rev Psychol

    (2008)
  • G.F. Koob

    Allostatic view of motivation: implications for psychopathology

  • D.O. Hebb

    Textbook of psychology

    (1972)
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