Involvement of κ-Opioid and Endocannabinoid System on Salvinorin A-Induced Reward

Braida, Daniela; Limonta, Valeria; Capurro, Valeria; Fadda, Paola; Rubino, Tiziana; Mascia, Paola; Zani, Alessia; Gori, E; Fratta, Walter; Parolaro, Daniela; Sala, Mariaelvina

doi:10.1016/j.biopsych.2007.07.020

Cited by 98 publications

(109 citation statements)

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“…Indirect actions on dopaminergic (Zhang et al, 2005), noradrenergic (Grilli et al, 2009), and endocannabinoid (Braida et al, 2007(Braida et al, , 2008 systems have also been characterized. Combined, the potential for a rapid release of dopamine (DA) within the reward circuitry of the nucleus accumbens might suggest the potential for drug reinforcement behavior with salvinorin NEUROPHARMACOLOGY OF SALVINORIN A 321 A.…”

Section: B Pharmacokinetic Properties Of Salvinorin Amentioning

confidence: 99%

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Neuropharmacology of the Naturally Occurring κ-Opioid Hallucinogen Salvinorin A

2011

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Section: B Pharmacokinetic Properties Of Salvinorin Amentioning

confidence: 99%

“…A study by Braida et al (2008), conducted in rats, suggests that the actions of salvinorin A on extracellular DA and CPP may be more complex than previously appreciated. In this study, salvinorin A was administered to rats over a broad range of doses (0.05-160 g/kg i.p.).…”

Section: Studies Examining Stress Mood and Rewardmentioning

confidence: 99%

Neuropharmacology of the Naturally Occurring κ-Opioid Hallucinogen Salvinorin A

2011

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“…A few investigators have recently examined salvinorin A in animal models of drug-induced reward, including conditioned place preference and intracerebroventricular (i.c.v.) self-administration (Zhang et al 2005;Braida et al 2007;Braida et al 2008). The results of these studies suggest that high doses of salvinorin A have aversive effects, although low doses may exert rewarding effects.…”

mentioning

confidence: 99%

“…The results of these studies suggest that high doses of salvinorin A have aversive effects, although low doses may exert rewarding effects. Interestingly, Braida et al (2008) reported that the reinforcing effects of low salvinorin A doses were attenuated by the CB1 antagonist rimonabant (1 mg/kg) as well as the KOP antagonist, nor-BNI (10 mg/kg). Using in vivo microdialysis techniques, Braida et al (2008) also observed that a low dose of salvinorin A (40 μg/kg) increased extracellular dopamine levels by approximately 150% in the NAc shell.…”

mentioning

confidence: 99%

“…Interestingly, Braida et al (2008) reported that the reinforcing effects of low salvinorin A doses were attenuated by the CB1 antagonist rimonabant (1 mg/kg) as well as the KOP antagonist, nor-BNI (10 mg/kg). Using in vivo microdialysis techniques, Braida et al (2008) also observed that a low dose of salvinorin A (40 μg/kg) increased extracellular dopamine levels by approximately 150% in the NAc shell. This finding is in contrast to previous findings that higher doses of salvinorin A decreased NAc DA levels (Zhang et al 2005).…”

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Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats

et al. 2009

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Background and rationale Research interests regarding the psychopharmacology of salvinorin A have been motivated by the recreational use and widespread media focus on the hallucinogenic plant, Salvia divinorum. Additionally, kappa opioid (KOP) receptor ligands may have therapeutic potential in the treatment of some neuropsychiatric conditions, including drug dependence and mood disorders. Salvinorin A is a selective KOP agonist, but only a few studies have explored the discriminative stimulus effects of this compound. Objective This study compared the discriminative stimulus effects of salvinorin A and two synthetic derivatives of salvinorin B to the KOP agonists, U69,593 and U50,488. Materials and methods Sixteen male Sprague-Dawley rats trained to discriminate U69,593 (0.13 mg/kg, s.c., N=8) or U50,488 (3.0 mg/kg, i.p., N=8) under a fixed-ratio 20 schedule of food reinforcement were administered substitution tests with salvinorin A (0.125-3.0 mg/kg, i.p.). The animals trained to discriminate U69,593 were also administered substitution tests with salvinorin B ethoxymethyl ether (0.005-0.10 mg/kg, i.p.) and salvinorin B methoxymethyl ether (0.03-0.10 mg/kg, i.p.). Another eight rats were trained to discriminate 2.0 mg/kg salvinorin A and tested with U69,593 (0.04-0.32 mg/kg) and U50,488 (0.4-3.2 mg/kg). Results Salvinorin A and both synthetic derivatives of salvinorin B substituted completely for U69,593. Additionally, cross-generalization was observed between salvinorin A and both KOP agonists.Conclusion These findings support previous reports indicating that the discriminative stimulus effects of salvinorin A are mediated by kappa receptors. Future studies may assist in the development and screening of salvinorin A analogs for potential pharmacotherapy.

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New Drugs of Abuse

et al. 2014

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Drug abuse is a common problem and growing concern in the United States, and over the past decade, novel or atypical drugs have emerged and have become increasingly popular. Recognition and treatment of new drugs of abuse pose many challenges for health care providers due to lack of quantitative reporting and routine surveillance, and the difficulty of detection in routine blood and urine analyses. Furthermore, street manufacturers are able to rapidly adapt and develop new synthetic isolates of older drugs as soon as law enforcement agencies render them illegal. In this article, we describe the clinical and adverse effects and purported pharmacology of several new classes of drugs of abuse including synthetic cannabinoids, synthetic cathinones, salvia, desomorphine, and kratom. Because many of these substances can have severe or life-threatening adverse effects, knowledge of general toxicology is key in recognizing acute intoxication and overdose; however, typical toxidromes (e.g., cholinergic, sympathomimetic, opioid, etc.) are not precipitated by many of these agents. Medical management of patients who abuse or overdose on these drugs largely consists of supportive care, although naloxone may be used as an antidote for desomorphine overdose. Symptoms of aggression and psychosis may be treated with sedation (benzodiazepines, propofol) and antipsychotics (haloperidol or atypical agents such as quetiapine or ziprasidone). Other facets of management to consider include treatment for withdrawal or addiction, nutrition support, and potential for transmission of infectious diseases.

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Involvement of κ-Opioid and Endocannabinoid System on Salvinorin A-Induced Reward

Cited by 98 publications

References 42 publications

Neuropharmacology of the Naturally Occurring κ-Opioid Hallucinogen Salvinorin A

Neuropharmacology of the Naturally Occurring κ-Opioid Hallucinogen Salvinorin A

Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats

New Drugs of Abuse

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