Animal Models of Alcoholism: Neurobiology of High Alcohol-Drinking Behavior in Rodents

McBride, William J.; Li, Ting Kai

doi:10.1615/critrevneurobiol.v12.i4.40

Cited by 575 publications

(470 citation statements)

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“…In the previous studies, we have found that 15 non-contingent presentations of the alcohol-associated stimulus complex produced immediate reinstatement of alcohol-seeking behavior (eg Bienkowski et al, 2000). In aggregate, our behavioral observations confirm that both alcohol-paired context and discrete cues may have incentive motivational properties for rats with alcohol self-administration history (McBride and Li, 1998;Le and Shaham, 2002;McBride et al, 2002).…”

Section: Pattern Of C-fos Activation In the Amygdala: A Role In Plastsupporting

confidence: 82%

Alcohol Relapse Induced by Discrete Cues Activates Components of AP-1 Transcription Factor and ERK Pathway in the Rat Basolateral and Central Amygdala

Radwańska

Wróbel

Korkosz

et al. 2007

Neuropsychopharmacol

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Alcohol-related cues may induce relapse to heavy alcohol drinking and promote molecular adaptations in discrete brain regions. An exact nature of these molecular alterations is still unknown. In the present study, rats trained to self-administer ethanol were tested for cueinduced reinstatement of ethanol seeking after 30 days of abstinence. Next, a detailed immunocytochemical analysis of c-Fos activation was performed within seven nuclei of the amygdala. In the second experiment, c-Fos activation after reinstatement of ethanol seeking induced by discrete cues was compared with the activation pattern of its putative partner (c-Jun) and regulators (extracellular signalregulated kinases and c-Jun N-terminal kinases). Reexposure to ethanol-associated context cues (an extinction session) potentiated c-Fos expression within the basolateral and central amygdala. Repeated presentation of ethanol-associated discrete cues in an extinction/ reinstatement session led to even stronger c-Fos activation in the latter nuclei. In the second experiment, reexposure to the ethanolassociated context and discrete cues activated both c-Jun and extracellular signal-regulated kinases (ERK1/2) in the basolateral amygdala. Our observations suggest that the basolateral and central amygdala may be specifically involved in alcohol-seeking behavior induced by discrete cues.

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Section: Pattern Of C-fos Activation In the Amygdala: A Role In Plastsupporting

confidence: 82%

Alcohol Relapse Induced by Discrete Cues Activates Components of AP-1 Transcription Factor and ERK Pathway in the Rat Basolateral and Central Amygdala

Radwańska

Wróbel

Korkosz

et al. 2007

Neuropsychopharmacol

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“…The animals selectively bred for excessive drinking show many of the characteristics of human alcoholics such as high alcohol intake, a generalized decreased sensitivity to alcohol, and drinking to the point of showing withdrawal effects upon cessation of drinking (McBride and Li 1998). Studies with inbred strains of mice allow for crossing and the identification of specific gene loci linked to a given trait by use of quantitative trait locus analysis (Phillips et al 1994).…”

Section: Animal Genetic Studiesmentioning

confidence: 99%

Drug Addiction, Dysregulation of Reward, and Allostasis

Koob

Moal

2001

Neuropsychopharmacology

2,500

1,932

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This paper reviews recent developments in the neurocircuitry and neurobiology of addiction from a perspective of allostasis. A model is proposed for brain changes that occur during the development of addiction that explain the persistent vulnerability to relapse long after drug-taking has ceased. Addiction is presented as a cycle of spiralling dysregulation of brain reward systems that progressively increases, resulting in the compulsive use and loss of control over drug-taking. The development of addiction recruits different sources of reinforcement, different neuroadaptive mechanisms, and different neurochemical changes to dysregulate the brain reward system. Counteradaptive processes such as opponent-process that are part of normal homeostatic limitation of reward function fail to return within the normal homeostatic range and are hypothesized to form an allostatic state. Allostasis from the addiction perspective is defined as the process of maintaining apparent reward function stability by changes in brain reward mechanisms. The allostatic state represents a chronic deviation of reward set point and is fueled not only by dysregulation of reward circuits per se, but also by the activation of brain and hormonal stress responses. The manifestation of this allostatic state as compulsive drugtaking and loss of control over drug-taking is hypothesized to be expressed through activation of brain circuits involved in compulsive behavior such as the cortico-striatal-thalamic loop. The view that addiction is the pathology that results from an allostatic mechanism using the circuits established for natural rewards provides a realistic approach to BACKGROUNDDrug addiction is a chronically relapsing disorder that is defined by two major characteristics: a compulsion to take the drug with a narrowing of the behavioral repertoire toward excessive drug intake, and a loss of control in limiting intake (American Psychiatric Association 1994; World Health Organization 1992). An important challenge for neurobiological research is to understand the neuroadaptive differences between controlled drug use and loss of control, and by extension, the molecular, cellular and system processes that lead to addiction (Koob and Le Moal 1997).Animal models are critical for understanding the neuropharmacological mechanisms involved in the development of addiction. While there are no complete animal models of addiction, animal models do exist for many elements of the syndrome. These elements can be derived from symptoms or diagnostic criteria for addiction or conceptual frameworks such as different sources of reinforcement (American Psychiatric Association 1994; World Health Organization 1992). Linking neu- 24 , NO . 2 ropharmacological events to animal models can occur at multiple levels of analysis -molecular, cellular and system -and it will only be the integration of these changes across dimensions of analysis that will allow a full understanding of the neurobiology of drug addiction.Advances in neuroscience research are rapidly unr...

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“…Animal models based on selective breeding for excessive ethanol drinking have demonstrated a utility for identifying and validating novel alcoholism treatment targets (McBride and Li, 1998). The alcohol-preferring AA (Alko Alcohol) and the alcohol-avoiding ANA (Alko Non-Alcohol) rat lines are among the best-established selection-based models, and have been bidrectionally bred for high and low alcohol consumption, respectively, for over 90 generations (Sinclair et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Genetic Impairment of Frontocortical Endocannabinoid Degradation and High Alcohol Preference

Hansson

Bermúdez‐Silva²,

Malinen

et al. 2006

Neuropsychopharmacol

148

155

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Endocannabinoid signaling has recently been implicated in ethanol-seeking behavior. We analyzed the expression of endocannabinoidrelated genes in key brain regions of reward and dependence, and compared them between the alcohol-preferring AA (Alko Alcohol) and nonpreferring ANA (Alko Non-Alcohol) rat lines. A decreased expression of fatty acid amidohydrolase (FAAH), the main endocannabinoid-degrading enzyme, was found in prefrontal cortex (PFC) of AA rats, and was accompanied by decreased enzyme activity in this region. Binding of the endocannabinoid-cannabinoid 1 (CB1) receptor ligand 3 [H]SR141716A, and [35S]GTPgS incorporation stimulated by the CB1 agonist WIN 55,212-2 were downregulated in the same area. Together, this suggests an overactive endocannabinoid transmission in the PFC of AA animals, and a compensatory downregulation of CB1 signaling. The functional role of impaired FAAH function for alcohol self-administration was validated in two independent ways. The CB1 antagonist SR141716A potently and dose-dependently suppressed self-administration in AA rats when given systemically, or locally into the PFC, but not in the striatum. Conversely, intra-PFC injections of the competitive FAAH inhibitor URB597 increased ethanol self-administration in nonselected Wistar rats. These results show for the first time that impaired FAAH function may confer a phenotype of high voluntary alcohol intake, and point to a FAAH both as a potential susceptibility factor and a therapeutic target.

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Animal Models of Alcoholism: Neurobiology of High Alcohol-Drinking Behavior in Rodents

Cited by 575 publications

References 0 publications

Alcohol Relapse Induced by Discrete Cues Activates Components of AP-1 Transcription Factor and ERK Pathway in the Rat Basolateral and Central Amygdala

Alcohol Relapse Induced by Discrete Cues Activates Components of AP-1 Transcription Factor and ERK Pathway in the Rat Basolateral and Central Amygdala

Drug Addiction, Dysregulation of Reward, and Allostasis

Genetic Impairment of Frontocortical Endocannabinoid Degradation and High Alcohol Preference

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