Behavioural and neurochemical assessment of salvinorin A abuse potential in the rat

Serra, Valeria; Fattore, Liana; Scherma, María; Collu, Roberto; Spano, Maria Sabrina; Fratta, Walter; Fadda, Paola

doi:10.1007/s00213-014-3641-z

Cited by 20 publications

(16 citation statements)

References 42 publications

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“…Acute and chronic effects of salvinorin A on dopaminergic systems may also differ ( Gehrke et al, 2008 ), of possible relevance to repeated users of salvinorin A-containing products. Paradoxically, some studies have reported that relatively smaller salvinorin A doses cause a detectable enhancement of dopamine dialysate levels ( Braida et al, 2008 ; Serra et al, 2015 ). The differential mechanisms involved in this latter effect have not been fully elucidated.…”

Section: Salvinorin a Effects In Preclinical Assays For Neuropsychiatmentioning

confidence: 99%

Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders

Butelman

Kreek

2015

Front. Pharmacol.

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Salvinorin A is a potent hallucinogen, isolated from the ethnomedical plant Salvia divinorum. Salvinorin A is a selective high efficacy kappa-opioid receptor (KOPr) agonist, and thus implicates the KOPr system and its endogenous agonist ligands (the dynorphins) in higher functions, including cognition and perceptual effects. Salvinorin A is the only selective KOPr ligand to be widely available outside research or medical settings, and salvinorin A-containing products have undergone frequent non-medical use. KOPr/dynorphin systems in the brain are known to be powerful counter-modulatory mechanisms to dopaminergic function, which is important in mood and reward engendered by natural and chemical reinforcers (including drugs of abuse). KOPr activation (including by salvinorin A) can thus cause aversion and anhedonia in preclinical models. Salvinorin A is also a completely new scaffold for medicinal chemistry approaches, since it is a non-nitrogenous neoclerodane, unlike other known opioid ligands. Ongoing efforts have the goal of discovering novel semi-synthetic salvinorin analogs with potential KOPr-mediated pharmacotherapeutic effects (including partial agonist or biased agonist effects), with a reduced burden of undesirable effects associated with salvinorin A.

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Section: Salvinorin a Effects In Preclinical Assays For Neuropsychiatmentioning

confidence: 99%

Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders

Butelman

Kreek

2015

Front. Pharmacol.

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“…An important consideration is the interaction of the endocannabinoid and its cannabinoid CB1 receptor with KOP in the pathophysiology of mood disorders and anxiety [52,53] . Upon with influences unlike those of other κ agonists [3] .…”

Section: Kop In Depression and Anxietymentioning

confidence: 99%

Kappa Opioid System Involvement in Mood and Anxiety Disorders

Taylor

Huffman

2017

International Journal of Neurology Research

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Current interest in opioid drugs is directed mostly on morphinelike drugs that activate the μ opioid peptide (MOP) system and induce euphoria and, potentially, addiction. Less attention has been paid to the κ opioid peptide (KOP) system, likely because drugs that activate the KOP system have low abuse potential. Indeed, activation of the KOP system often is reported to have effects on brain and behavior that are opposite to MOP activation. The literature suggests that dynorphin and its κ receptor are, indeed, unique among the opioids. That uniqueness has generated interest in our laboratory. We have taken a different approach to understanding the KOP system. Rather than focusing on drug abuse, we have adopted mood and anxiety as a model for investigation of the KOP system. The assumption is that clarification of the underlying mechanisms and behavioral outcomes of κ agonists and antagonists will help inform the KOP system for other situations, including drug use and abuse. This review will highlight the basis for our fascination with KOP and the κ receptor.

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“…Preclinical findings include that, as with most other hallucinogens, lab animals failed to readily self- administer Salv A [ 88 ]. Indeed, results with animal models suggest that the drug reduces activity of DA in the BRS and even is aversive [ 88 ].…”

Section: The Special Case Of Salvinorin Amentioning

confidence: 99%

Kappa Opioids, Salvinorin A and Major Depressive Disorder

Taylor¹,

Manzella

2016

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Opioids are traditionally associated with pain, analgesia and drug abuse. It is now clear, however, that the opioids are central players in mood. The implications for mood disorders, particularly clinical depression, suggest a paradigm shift from the monoamine neurotransmitters to the opioids either alone or in interaction with monoamine neurons. We have a special interest in dynorphin, the last of the major endogenous opioids to be isolated and identified. Dynorphin is derived from the Greek word for power, dynamis, which hints at the expectation that the neuropeptide held for its discoverers. Yet, dynorphin and its opioid receptor subtype, kappa, has always taken a backseat to the endogenous b-endorphin and the exogenous morphine that both bind the mu opioid receptor subtype. That may be changing as the dynorphin/ kappa system has been shown to have different, often opposite, neurophysiological and behavioral influences. This includes major depressive disorder (MDD). Here, we have undertaken a review of dynorphin/ kappa neurobiology as related to behaviors, especially MDD. Highlights include the unique features of dynorphin and kappa receptors and the special relation of a plant-based agonist of the kappa receptor salvinorin A. In addition to acting as a kappa opioid agonist, we conclude that salvinorin A has a complex pharmacologic profile, with potential additional mechanisms of action. Its unique neurophysiological effects make Salvinorina A an ideal candidate for MDD treatment research.

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Behavioural and neurochemical assessment of salvinorin A abuse potential in the rat

Abstract: Salvinorin A differs from other commonly abused compounds since although it affects accumbal dopamine transmission, yet it is unable, at least at the tested doses, to sustain stable intravenous self-administration behaviour.

Cited by 20 publications

References 42 publications

Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders

Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders

Kappa Opioid System Involvement in Mood and Anxiety Disorders

Kappa Opioids, Salvinorin A and Major Depressive Disorder

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