Locomotor stimulant effects of acute and repeated intrategmental injections of salsolinol in rats: role of μ-opioid receptors

Hipólito, Lucía; Sánchez-Catalán, María José; Zornoza, Teodoro; Polache, Ana; Granero, Luis

doi:10.1007/s00213-009-1751-9

Cited by 49 publications

(48 citation statements)

References 49 publications

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“…Thus, clear physiological effects are observed when only one side is injected. In line with this view, in a previous study (Quintanilla et al 2014), we injected unilaterally the same dose of (RS)-SAL (30 pmol) that (Hipólito et al 2010(Hipólito et al , 2011 had injected bilaterally, obtaining the same results on locomotor activity and CPP.…”

Section: Drug Microinjection Proceduressupporting

confidence: 78%

“…Ammonium acetate was from Merck (Darmstadt, Germany) and triethylamine was from Sigma (St. Louis, MO, USA). For intracerebral administration, SAL was diluted with artificial cerebrospinal fluid (aCSF, containing 120.0 mM NaCl, 4.8 mM KCl, 1.2 mM KH2PO4, 1.2 mM MgSO4, 25.0 mM NaHCO3, 1.2 mM CaCl2, 10 mM d-glucose and 0.2 mM ascorbate, pH 6.5) for slow injection (1.0 μl) into the VTA (30 pmol/μl), according to Hipólito et al (2010Hipólito et al ( , 2011.…”

Section: Drugs and Solutionsmentioning

confidence: 99%

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(R)-Salsolinol, a product of ethanol metabolism, stereospecifically induces behavioral sensitization and leads to excessive alcohol intake

et al. 2015

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Ethanol is oxidized in the brain to acetaldehyde, which can condense with dopamine to generate (R/S)-salsolinol [(RS)-SAL]. Racemic salsolinol [(RS)-SAL] is self-infused by rats into the posterior ventral tegmental area (VTA) at significantly lower concentrations than those of acetaldehyde, suggesting that (RS)-SAL is a most active product of ethanol metabolism. Early studies showed that repeated intraperitoneal or intra-VTA administration of (RS)-SAL (10 mg/kg) induced conditioned place preference, led to locomotor sensitization and increased voluntary ethanol consumption. In the present study, we separated the (R)- and (S)-enantiomers from a commercial (RS)-SAL using a high-performance liquid chromatography with electrochemical detection system fitted with a β-cyclodextrin-modified column. We injected (R)-SAL or (S)-SAL (30 pmol/1.0 μl) into the VTA of naïve UChB rats bred as alcohol drinkers to study whether one or both SAL enantiomers are responsible for the motivated behavioral effects, sensitization and increase in voluntary ethanol intake. The present results show that repeated administration of (R)-SAL leads to (1) conditioned place preference; (2) locomotor sensitization; and (3) marked increases in binge-like ethanol intake. Conversely, (S)-SAL did not influence any of these parameters. Overall, data indicate that (R)-SAL stereospecifically induces motivational effects, behavioral sensitization and increases ethanol intake.

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Section: Drug Microinjection Proceduressupporting

confidence: 78%

Section: Drugs and Solutionsmentioning

confidence: 99%

(R)-Salsolinol, a product of ethanol metabolism, stereospecifically induces behavioral sensitization and leads to excessive alcohol intake

et al. 2015

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“…Behavioral and neurochemical studies have shown that acetaldehyde and salsolinol have stimulating properties into the pVTA (Rodd-Henricks et al, 2002;Rodd et al, 2008;Sanchez-Catalan et al, 2009;Hipolito et al, 2010Hipolito et al, , 2011. Accordingly, it has been observed that they enhance the activity of the pVTA dopamine neurons (Melis et al, 2007;.…”

Section: Electrophysiologicalmentioning

confidence: 97%

The antero-posterior heterogeneity of the ventral tegmental area

et al. 2014

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“…Additionally, SAL has been shown to possess a high affinity for the μ (MOR) opioid receptor (Airaksinen et al, 1984). SAL-induced locomotor activity, conditioned place preference, and stimulated DA release in the AcbSh can be reduced by microinjections of MOR antagonists into the posterior VTA (Hipolito et al, 2010(Hipolito et al, , 2011.…”

Section: Alcohol Acetaldehyde and Acetaldehyde Productsmentioning

confidence: 99%

“…Thus, the reinforcing actions of all 3 compounds in the posterior VTA is dependent upon VTA DA neuronal activity, since quinpirole would act to stimulate D 2 autoreceptors (reduction in DA activity). SAL microinjected into the VTA will produce a conditioned place preference (Hipolito et al, 2010(Hipolito et al, , 2011. Reverse microdialysis of SAL has been shown to modulate DA levels within the Acb (Hipolito et al, 2009).…”

Section: Behavioral Pharmacology Of Acetaldehyde Within the Mesolimbimentioning

confidence: 99%

What is in that Drink: The Biological Actions of Ethanol, Acetaldehyde, and Salsolinol

Deehan

Brodie

Rodd

2011

Behavioral Neurobiology of Alcohol Addiction

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Alcohol abuse and alcoholism represent substantial problems that affect a large portion of individuals throughout the world. Extensive research continues to be conducted in an effort to identify the biological basis of the reinforcing properties of alcohol in order to develop effective pharmacotherapeutic and behavioral interventions. One theory that has developed within the alcohol field over the past 4 decades postulates that the reinforcing properties of alcohol are due to the action of the metabolites/products of alcohol within the central nervous system (CNS). The most extreme version of this theory suggests that the biologically active metabolites/products of alcohol, created from the breakdown from alcohol, are the ultimate source of the reinforcing properties of alcohol. The contrary theory proposes that the reinforcing properties of alcohol are mediated completely through the interaction of the ethanol molecule with several neurochemical systems within the CNS. While there are scientific findings that offer support for both of these stances, the reinforcing properties of alcohol are most likely generated through a complex series of peripheral and central effects of both alcohol and its metabolites. Nonetheless, the development of a greater understanding for how the metabolites/products of alcohol contribute to the reinforcing properties of alcohol is an important factor in the development of efficacious pharmacotherapies for alcohol abuse and alcoholism. This chapter is intended to provide a historical perspective of the role of acetaldehyde (the first metabolite of alcohol) in alcohol reinforcement as well as review the basic research literature on the effects of acetaldehyde (and acetaldehyde metabolites/products) within the CNS and how these function with regard to alcohol reward.

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Locomotor stimulant effects of acute and repeated intrategmental injections of salsolinol in rats: role of μ-opioid receptors

Abstract: Salsolinol induces locomotor activity and motor sensitization after intra-VTA administration. Moreover, the implication of the mu-opioid receptors was shown since the treatment with naltrexone or beta-FNA was able to suppress the salsolinol effects.

Cited by 49 publications

References 49 publications

(R)-Salsolinol, a product of ethanol metabolism, stereospecifically induces behavioral sensitization and leads to excessive alcohol intake

(R)-Salsolinol, a product of ethanol metabolism, stereospecifically induces behavioral sensitization and leads to excessive alcohol intake

The antero-posterior heterogeneity of the ventral tegmental area

What is in that Drink: The Biological Actions of Ethanol, Acetaldehyde, and Salsolinol

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