Intra‐amygdala Muscimol Decreases Operant Ethanol Self‐administration in Dependent Rats

Roberts, Amanda J.; Cole, Maury; Koob, George F.

doi:10.1111/j.1530-0277.1996.tb01125.x

Cited by 325 publications

(297 citation statements)

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“…As such, these effects may reflect changes in the activity of the same mesocorticolimbic system (midbrain-forebrain system) implicated in the positive reinforcing effects of drugs and can last up to 72 hours depending on the drug and dose administered (Legault and Wise 1994;Leith and Barrett 1976; Koob 1991, 1992;Parsons et al 1995;Schulteis et al 1994) ( Table 2). Examples of such changes at the neurochemical level include decreases in dopaminergic and serotonergic transmission in the nucleus accumbens during drug withdrawal as measured by in vivo microdialysis (Parsons et al 1995;Weiss et al 1992b), increased sensitivity of opioid receptor transduction mechanisms in the nucleus accumbens during opiate withdrawal (Stinus et al 1990), decreased GABAergic and increased NMDA glutamatergic transmission during alcohol withdrawal (Fitzgerald and Nestler 1995;Roberts et al 1996;, and differential regional changes in nicotine receptor function (Collins et al. 1990; Dani and Heinemann 1996) (Table 3).…”

Section: Neural Substrates Of Motivational Withdrawalmentioning

confidence: 99%

“…There is enhanced sensitivity of alcohol-dependent rats to GABA agonists during acute withdrawal (Roberts et al 1996), and the CRF systems in the central nucleus of the amygdala are activated during acute alcohol, opioid, THC and cocaine withdrawal (Merlo-Pich et al 1995).…”

Section: Extended Amygdala: a Common Substrate For Allostatic Changesmentioning

confidence: 99%

“…The following definitions apply: allostasis, the process of achieving stability through change; allostatic state, a state of chronic deviation of the regulatory system from its normal (homeostatic) operating level; allostatic load, the cost to the brain and body of the deviation, accumulating over time, and reflecting in many cases pathological states and accumulation of damage. during alcohol withdrawal (Fitzgerald and Nestler 1995;Roberts et al 1996;, and differential regional changes (reward system versus nonreward systems) in nicotine receptor function during nicotine addiction (Collins et al 1990;Dani and Heinemann 1996).…”

Section: Neurosubstrates Of Allostatic Neuroadaptationmentioning

confidence: 99%

“…24, NO. 2 during alcohol withdrawal (Fitzgerald and Nestler 1995;Roberts et al 1996;, and differential regional changes (reward system versus nonreward systems) in nicotine receptor function during nicotine addiction (Collins et al 1990; Dani and Heinemann 1996). …”

mentioning

confidence: 99%

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Drug Addiction, Dysregulation of Reward, and Allostasis

Koob

Moal

2001

Neuropsychopharmacology

2,561

1,962

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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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Section: Neural Substrates Of Motivational Withdrawalmentioning

confidence: 99%

Section: Extended Amygdala: a Common Substrate For Allostatic Changesmentioning

confidence: 99%

Section: Neurosubstrates Of Allostatic Neuroadaptationmentioning

confidence: 99%

mentioning

confidence: 99%

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Drug Addiction, Dysregulation of Reward, and Allostasis

Koob

Moal

2001

Neuropsychopharmacology

2,561

1,962

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“…Therefore, the purpose of this experiment was to examine the effects of chronic ethanol exposure and a two week period of abstinence on the alcohol deprivation effect and its recovery to stable baseline responding. In addition, these rats were scored for ethanol withdrawal severity in order to confirm that the ethanol vapor chamber protocol was producing physical dependence as had been found previously (Roberts et al 1996).Twelve rats were trained to lever press for 10% ethanol and then half were exposed to ethanol vapor ( n ϭ 6) and half were exposed to air ( n ϭ 6) for two weeks. Eight hours following removal from the chambers, the rats were tested for ethanol withdrawal symptoms.…”

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confidence: 99%

Excessive Ethanol Drinking Following a History of Dependence Animal Model of Allostasis

Roberts

Heyser

Cole

et al. 2000

Neuropsychopharmacology

324

326

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Self-administration Excessive drinking of ethanol in animals can be produced by a number of factors including altering palatability, genetics, and history of consumption. There is evidence that certain symptoms of withdrawal can persist for a number of weeks or even months following chronic ethanol exposure in humans (Kissin 1979;Begleiter and Porjesz 1979;Alling et al. 1982;Roelofs 1985;Grant et al. 1987) as well as in animals (Begleiter and Porjesz 1979). In human alcoholics, one of the factors leading to excessive drinking is the use of alcohol to relieve or avoid withdrawal symptoms (U.S. Department of Health and Human Services 1990). Fatigue and tension persisted for approximately five weeks following withdrawal in a group of 68 chronic alcoholics (Alling et al. 1982), and periods of hyperventilatory symptomology and anxiety (as determined by the Spielberger State-Trait Anxiety Inventory, a self-report inventory), which correlated with intensity of alcohol craving, were reported for up to nine months following withdrawal in a group of 37 chronic alcoholics (Roelofs 1985).In a larger cohort of 312 abstinent alcoholics, 20-25% of them showed signs of anxiety and depression, as determined from the Symptom Check-List 90 (self-report inventory with coverage of areas of symptomology and psychopathology) six months to two years following withdrawal (De Soto et al. 1985). In a follow-up study, it was shown that distress-related symptoms correlated with relapse in alcoholics who were abstinent for less than two years (De Soto et al. 1989). The more pro- Received March 2, 1999; revised August 25, 1999; accepted December 6, 1999. 582 A.J. Roberts et al. N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 22 , NO . 6 tracted symptoms tended to be subacute, were often affective in nature, and appeared to precede relapses into uncontrolled alcohol drinking. For example, depression and anxiety associated with withdrawal were found to provoke drinking in 83 of 100 male alcoholics who experienced these symptoms (Hershon 1977). These patients reported that they drank alcoholic beverages when they experienced anxiety and depressed mood. In another study, both male and female alcoholics reported negative emotions as the most common trigger of relapse (Annis et al. 1998). The clinical literature suggests that alterations in affective state persist for quite some time following alcohol withdrawal and may actually be partly responsible for some relapse episodes in alcoholics.Potential rodent models of excessive ethanol drinking include the alcohol deprivation effect in nondependent animals, ethanol self-administration in dependent withdrawing animals, and ethanol self-administration in animals with a history of dependence following periods of abstinence. The alcohol deprivation effect is a transient increase in ethanol self-administration in animals following periods of abstinence from ethanol for several days to several weeks (Sinclair and Senter 1967;Spanagel et al. 1996;Heyser et al. 1997;Hölter et al. 1998). This increase in e...

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Vapor Inhalation of Alcohol in Rats

et al. 2008

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Alcohol dependence constitutes a neuroadaptive state critical for understanding alcoholism, and various methods have been utilized to induce alcohol dependence in animals, one of which is alcohol vapor exposure. Alcohol vapor inhalation provides certain advantages over other chronic alcohol exposure procedures that share the ultimate goal of producing alcohol dependence in rats. Chronic alcohol vapor inhalation allows the experimenter to control the dose, duration, and pattern of alcohol exposure. Also, this procedure facilitates testing of somatic and motivational aspects of alcohol dependence. Chronic exposure to alcohol vapor produces increases in alcohol-drinking behavior, increases in anxiety-like behavior, and reward deficits in rats. Alcohol vapor inhalation as a laboratory protocol is flexible, and the parameters of this procedure can be adjusted to accommodate the specific aims of different experiments. This unit describes the options available to investigators using this procedure for dependence induction, when different options are more or less appropriate, and the implications of each.

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Intra‐amygdala Muscimol Decreases Operant Ethanol Self‐administration in Dependent Rats

Cited by 325 publications

References 47 publications

Drug Addiction, Dysregulation of Reward, and Allostasis

Drug Addiction, Dysregulation of Reward, and Allostasis

Excessive Ethanol Drinking Following a History of Dependence Animal Model of Allostasis

Vapor Inhalation of Alcohol in Rats

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