Chapter 3 - Neurocircuitry of alcohol addiction: synthesis from animal models
Section snippets
Definitions and conceptual framework for neurocircuitry of alcoholism
Alcoholism has many definitions that vary from social frameworks to a psychiatric framework. Alcoholism, more generically drug addiction, can be defined as a chronically relapsing disorder characterized by: (1) compulsion to seek and take the drug (alcohol); (2) loss of control in limiting (alcohol) intake; and (3) emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability), reflecting a motivational withdrawal syndrome, when access to the drug (alcohol) is prevented
Animal models for compulsive alcohol seeking
Methods of inducing binge-like drinking with alcohol range from having animals drink alcohol solutions that are made extra palatable with the addition of a sweetener (Ji et al., 2008) to intermittent overnight access (Wise, 1973, Simms et al., 2010), to restricting intake to specific periods of the dark cycle (i.e., drinking-in-the-dark; Rhodes et al., 2005), to models that involve alcohol dependence in animals, such as alcohol vapor inhalation, intragastric alcohol infusion, and alcohol liquid
Animal models of motivation, withdrawal, and opponent process
The concept of motivation in addiction was inextricably linked with hedonic, affective, or emotional states in the context of temporal dynamics by Solomon's opponent process theory of motivation. Solomon and Corbit (1974) postulated that hedonic, affective, or emotional states, once initiated by drugs, are automatically modulated by the central nervous system with mechanisms that reduce the intensity of hedonic feelings. The a-process in drug use consists of positive hedonic responses, occurs
Neurocircuits for the binge/intoxication stage associated with alcoholism
Animal models for the acute reinforcing effects of alcohol and the use of selective antagonists for specific neurochemical systems have supported the hypothesis that alcohol at intoxicating doses has a wide but selective action on neurotransmitter systems in the brain reward systems. Neuropharmacologic studies have implicated multiple neurochemical systems in the acute reinforcing effects of alcohol, including γ-aminobutyric acid (GABA), opioid peptides, dopamine, serotonin, and glutamate (Fig.
Within-system neuroadaptations that contribute to the compulsivity associated with the dark side of alcoholism
Within-system neuroadaptations to chronic drug exposure include decreases in the function of the same neurotransmitter systems in the same neurocircuits implicated in the acute reinforcing effects of drugs of abuse. One prominent hypothesis is that dopamine systems are compromised in crucial phases of the addiction cycle, such as withdrawal and protracted abstinence. This decrease in dopamine function is hypothesized to lead to decreased motivation for non-drug-related stimuli and increased
Neural substrates for executive function deficits associated with alcoholism
The preoccupation/anticipation stage of the addiction cycle has long been hypothesized to be a key element of relapse in humans and defines addiction as a chronic relapsing disorder. Although often linked to the construct of craving, craving per se has been difficult to measure in human clinical studies (Tiffany et al., 2000) and often does not correlate with relapse. Nevertheless, the stage of the addiction cycle where the individual reinstates drug-seeking behavior after abstinence remains a
Compulsivity in alcoholism: an allostatic view
Compulsivity in alcoholism can derive from neurocircuitry changes at all three stages of the addiction cycle (Fig. 3.8). In the binge/intoxication stage, such changes involve neurocircuits that include enhanced incentive salience (Robinson and Berridge, 1993) and engagement of habit function (Everitt et al., 2008). In the withdrawal/negative affect stage, such changes involve neurocircuits involved in negative emotional states. In the preoccupation/anticipation stage, such changes involve
Acknowledgments
The author would like to thank Michael Arends and Mellany Santos for assistance with manuscript preparation and editing. Research was supported by National Institutes of Health grants AA006420, AA020608, and AA008459 from the National Institute on Alcohol Abuse and Alcoholism and the Pearson Center for Alcoholism and Addiction Research. This is publication number 24030 from The Scripps Research Institute.
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