Facilitation of brain stimulation reward byΔ 9-tetrahydrocannabinol

Gardner, Eliot L.; Paredes, William; Smith, Diane; Donner, Amy; Milling, C.; Cohen, Dana; Morrison, Dempsie B.

doi:10.1007/bf02431546

Cited by 210 publications

(113 citation statements)

References 19 publications

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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).…”

Section: Tetrahydrocannabinolsupporting

confidence: 53%

Drug Addiction, Dysregulation of Reward, and Allostasis

Koob

Moal

2001

Neuropsychopharmacology

2,544

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: Tetrahydrocannabinolsupporting

confidence: 53%

Drug Addiction, Dysregulation of Reward, and Allostasis

Koob

Moal

2001

Neuropsychopharmacology

2,544

1,962

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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: 72%

“…It has been confirmed that Δ 9 -THC shares many features with classical drugs of abuse, such as cocaine and heroin (for review see Gardner and Vorel, 1998;Tanda and Goldberg, 2003;Lupica et al, 2004). For example, THC lowers electrical brain-stimulation reward thresholds (Gardner et al, 1988), and increases the firing rate of ventral tegmental area (VTA) dopaminergic neurons projecting to the nucleus accumbens (French et al, 1997;Gifford et al, 1997), resulting in increased extracellular levels of dopamine in the nucleus accumbens (e.g., Chen et al, 1990;Tanda et al, 1997). It has also been shown that chronic cannabinoid administration leads to other significant neurobiological changes that resemble those already described for other drugs abused by humans (Rodriguez de Fonseca et al, 1997;Diana et al, 1998;Tanda et al, 1999;see Tanda and Goldberg, 2003 for review).…”

Section: Subjective and Motivational Effects Of Cannabinoidsmentioning

confidence: 99%

“…Most of the evidence for a role of endogenous opioid systems in the modulation of the reinforcing or rewarding effects of THC or cannabinoids is indirect and comes from behavioral studies of locomotion (Ghozland et al, 2002) or electrical brain stimulation reward (Gardner et al, 1989) or from in-vivo brain microdialysis studies in rodents (Chen et al, 1990;Tanda et al, 1997). More direct evidence for a role of opioid neurotransmitter systems in the modulation of the reinforcing effects of cannabinoids comes from recent rodent drug self-administration studies in which naloxone pretreatment reduced intravenous drug self-administration behavior maintained by the synthetic cannabinoid CB 1 receptor agonists WIN 55,212-2 and HU-210 (Navarro et al, 2001) and CP 55,940 (Braida et al, 2001a;.…”

Section: Self-administration Of Cannabinoids By Laboratory Animalsmentioning

confidence: 99%

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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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“…Third, THC is known to impact on aspects of reward processing by, for example, reducing reward thresholds for operant responding leading to brain-self-stimulation (Gardner et al, 1988;Gardner and Lowinson, 1991). Also, THC also has an indirect action on dopamine neurotransmission in the mesolimbic and mesocortical systems (Ameri, 1999;Gardner and Vorel, 1998;Tanda and Goldberg, 2003;Tanda et al, 1997), suggesting that the acute effects of THC include altered catecholamine activity within the corticolimbic pathways that mediate decision-making cognition (Scarna et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

The Effects of Low Doses of Δ-9 Tetrahydrocannabinol on Reinforcement Processing in the Risky Decision-Making of Young Healthy Adults

Rogers

Wakeley

Robson

et al. 2006

Neuropsychopharmacol

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Research suggests that risky decision-making is sensitive to neuromodulatory influences acting upon corticolimbic circuitry. However, while other evidence attests to effects of D-9 tetrahydrocannabinol (THC) on the activity of reward pathways, relatively little is known about the possible involvement of cannabinoid activity in risky choice. In this experiment, we examined the effects of a single sublingual 5 mg dose of THC on a test of risky decision-making (requiring choices between simultaneously presented gambles differing in their magnitude of gains, magnitude of losses and the probability with which these outcomes were delivered). Tests of non-normative decision-making involving risk-aversion when deciding between gains and risk-seeking choices when deciding between losses were also included. In all, 15 healthy adults were administered 5 mg THC and placebo in a double-blind, placebo-controlled, within-subject, crossover design. THC had three principal effects relative to placebo: (i) THC reduced choice of gambles with variable gains and losses, but increased choice of gambles with zero-expected value; (ii) THC reduced participants' attention towards losses when the probability of winning was low (and the probability of losing was high); and (iii) THC speeded participants' responses to gambles with large compared to small potential gains. These results suggest that THC mediates specific motivational processes and the processing of reinforcement cues during risky choice, perhaps reflecting altered CB 1 receptor or catecholamine activity within corticolimbic pathways.

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Facilitation of brain stimulation reward byΔ 9-tetrahydrocannabinol

Cited by 210 publications

References 19 publications

Drug Addiction, Dysregulation of Reward, and Allostasis

Drug Addiction, Dysregulation of Reward, and Allostasis

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

The Effects of Low Doses of Δ-9 Tetrahydrocannabinol on Reinforcement Processing in the Risky Decision-Making of Young Healthy Adults

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