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