Genetic differences in Δ9-tetrahydrocannabinol-induced facilitation of brain stimulation reward as measured by a rate-frequency curve-shift electrical brain stimulation paradigm in three different rat strains

Lepore, Marino; Liu, Xinhe; Savage, Virginia; Matalon, Daniel; Gardner, Eliot L.

doi:10.1016/0024-3205(96)00237-8

Cited by 114 publications

(94 citation statements)

References 20 publications

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“…animal strain) in rendering the addictive properties of cannabinoids manifest in behavioral protocols (see also below). Intriguingly, behavioural findings by Lepore et al (1996) closely parallel the neurochemical ones reported by the same group, with THC producing robust enhancement of both BSR and accumbal DA level in drug-preferring Lewis rats, a moderate BSR and accumbal DA level enhancement in drug-neutral Sprague-Dawley rats, and no effect in drug-resistant Fisher 344 strain (Chen et al, 1991;Gardner et al, 2002).…”

Section: Behavioural Evidencesupporting

confidence: 63%

“…Recently, a study from our laboratory have confirmed that, in line with the cannabinoidinduced enhancement of mesolimbic DA release and BSR threshold (Chen et al, 1991;Lepore et al, 1996), intravenous cannabinoid SA in rats also depends on the specific strain of animal used, such a behavior being clearly evident in Lister Hooded and Long Evans, but not Sprague-Dawley rats (Deiana et al, 2007). Moreover, cannabinoid intake by trained rats is significantly affected either by sex, females acquiring stable cannabinoid intake at higher rates and more rapidly than males, and by ovarian function, ovariectomised females being less sensible to cannabinoid rewarding effects than intact counterparts (Fattore et al, 2007b).…”

mentioning

confidence: 62%

“…More recently, the synthetic CB1-R agonists WIN 55,212-2 and CP 55,940 have also shown to increase the threshold for BSR (Vlachou et al, 2005), although lack of effects of CP 55,940 was reported by one study using similar experimental conditions (Arnold et al, 2001). Subsequent observation by Gardner and colleagues of the existence of strain differences in such a behavior (Lepore et al, 1996) deserves special mention, as it represents the first demonstration of the key role played by this feature (i.e. animal strain) in rendering the addictive properties of cannabinoids manifest in behavioral protocols (see also below).…”

Section: Behavioural Evidencementioning

confidence: 98%

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Neurobiological mechanisms of cannabinoid addiction

Fattore

Fadda

Spano

et al. 2008

Molecular and Cellular Endocrinology

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Please cite this article as: Fattore, L., Fadda, P., Spano, M.S., Pistis, M., Fratta, W., Neurobiological mechanisms of cannabinoid addiction, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 2 AbstractThe endocannabinoid system is implicated in the regulation of a variety of physiological processes, among which conditioning, motivation, habit forming, memory, learning, and cognition play pivotal roles in drug reinforcement and reward. In this article we will give a synopsis of last developments in research on cannabinoid actions on brain reward circuits coming from behavioral, neurochemical and electrophysiological studies. Central cannabinoid-induced effects as measured by animal models of addiction, in vivo cerebral microdialysis, in vitro and in vivo electrophysiological recording techniques, will be reviewed.Brain sites that have been implicated in the mediation of addictive cannabinoid properties include primarily the ventral tegmental area, the nucleus accumbens, and the medial prefrontal cortex, although the amygdala, the substantia nigra, the globus pallidus, and the hippocampus have also been shown to be critical structures mediating motivational and reinforcing effects of cannabinoids. Putative neurobiological mechanisms underlying these effects will be delineated.

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Section: Behavioural Evidencesupporting

confidence: 63%

mentioning

confidence: 62%

Section: Behavioural Evidencementioning

confidence: 98%

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Neurobiological mechanisms of cannabinoid addiction

Fattore

Fadda

Spano

et al. 2008

Molecular and Cellular Endocrinology

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“…Evidence for acute reinforcing effects of THC comes from studies of brain stimulation reward, place preference and intravenous self-administration. Reward thresholds are decreased by THC administration in rats upon acute administration (Gardner et al 1988;Lepore et al 1996), and THC also produces a place preference (Lepore et al 1995). THC increases dopamine in the shell of the nucleus accumbens similar to that observed with other major drugs of abuse (Tanda et al 1997).…”

mentioning

confidence: 53%

Drug Addiction, Dysregulation of Reward, and Allostasis

Koob

Moal

2001

Neuropsychopharmacology

2,548

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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“…These models include intracranial electrical self-stimulation techniques. Consistent with a role of cannabinoids in the motivational effects of other events that can function as rewards or reinforcers, it has been shown that THC lowers the threshold for electrical brain-stimulation reward in Lewis and Sprague-Dawley rat strains, and that withdrawal from a single administration of THC can elevate brain-stimulation reward thresholds (Gardner et al, 1988;1989;Lepore et al, 1996;Gardner and Vorel, 1998). However, these findings contrast with the lack of THC effects in the Fisher rat strain (Lepore et al, 1996), and the lack of effects of the synthetic CB1 receptor agonist CP 55,940 using the same procedure and a comparable range of doses (Arnold et al, 2001).…”

Section: Subjective and Motivational Effects Of Cannabinoidsmentioning

confidence: 74%

Self-administration of cannabinoids by experimental animals and human marijuana smokers

Justinová

Goldberg

Heishman

2005

Pharmacology Biochemistry and Behavior

115

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Drug self-administration behavior has been one of the most direct and productive approaches for studying the reinforcing effects of psychoactive drugs, which are critical in determining their abuse potential. Cannabinoids, which are usually abused by humans in the form of marijuana, have become the most frequently abused illicit class of drugs in the United States. The early elucidation of the structure and stereochemistry of delta-9-tetrahydrocannabinol (THC) in 1964, which is now recognized as the principal psychoactive ingredient in marijuana, activated cannabinoid research worldwide. This review examines advances in research on cannabinoid self-administration behavior by humans and laboratory animals. There have been numerous laboratory demonstrations of the reinforcing effects of cannabinoids in human subjects, but reliable self-administration of cannabinoids by laboratory animals has only recently been demonstrated. It has now been shown that strong and persistent self-administration behavior can be maintained in experimentally and drugnaïve squirrel monkeys by doses of THC comparable to those in marijuana smoke inhaled by humans. Furthermore, reinforcing effects of some synthetic CB 1 cannabinoid agonists have been recently reported using intravenous and intracerebroventricular self-administration procedures in rats and mice. These findings support previous conclusions that THC has a pronounced abuse liability comparable to other drugs of abuse under certain experimental conditions. Self-administration of THC by squirrel monkeys provides the most reliable animal model for human marijuana abuse available to date. This animal model now makes it possible to study the relative abuse liability of other natural and synthetic cannabinoids and to preclinically assess new therapeutic strategies for the treatment or prevention of marijuana abuse in humans.

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Genetic differences in Δ9-tetrahydrocannabinol-induced facilitation of brain stimulation reward as measured by a rate-frequency curve-shift electrical brain stimulation paradigm in three different rat strains

Cited by 114 publications

References 20 publications

Neurobiological mechanisms of cannabinoid addiction

Neurobiological mechanisms of cannabinoid addiction

Drug Addiction, Dysregulation of Reward, and Allostasis

Self-administration of cannabinoids by experimental animals and human marijuana smokers

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