Inhibition of acetaldehyde metabolism decreases acetylcholine release in medial frontal cortex of freely moving rats

Jamal, Mostofa; Ameno, Kiyoshi; Wang, Weihuan; Kumihashi, Mitsuru; Ameno, Setsuko; Uekita, Ikuo; Azuma, Shinji; Ijiri, Iwao

doi:10.1016/j.brainres.2005.01.049

Cited by 16 publications

(5 citation statements)

References 36 publications

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“… The average acetylcholine (ACh) levels (±SEM) in nM within the prefrontal cortex of rats. Basal value (Huang et al,2008; Ichikawa et al,2002a,b,c; Jamal et al,2005; Lacroix et al,2006; Li et al,2007); NEO 0.01 μM (Ago et al,2006; Sato et al,2007); NEO 0.05 μM (Passetti et al,2000); NEO 0.1 μM (Nair and Gudelsky,2004, 2005, 2006); NEO 0.3 μM (Biton et al,2007; Parada et al,1997); NEO 0.5 μM (Anzalone et al,2010; Giovannini et al,2005; Jansson et al,2004; Mark et al,1996; Mork et al,2009; Tellez et al,1999); NEO 1 μM (Hernandez et al,2008); NEO 5 μM (Laplante et al,2005); NEOBr 0.1 μM (Acquas et al,2000,2001a,b; Pisanu et al,2006; Verrico et al,2003); PHYS 10 μM (Izaki et al,2001); PHYSS 0.1 μM (Petkova‐Kirova et al,2008). …”

Section: Resultsmentioning

confidence: 99%

The impact of acetylcholinesterase inhibitors on the extracellular acetylcholine concentrations in the adult rat brain: A meta‐analysis

Noori

Fliegel

Brand

et al. 2012

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In vivo microdialysis has become a key method in investigating the dynamics of different neurotransmitter systems such as acetylcholine in the extracellular fluid. Depending on the sensitivity of the analytical method applied for measuring acetylcholine levels in brain dialysates, acetylcholinesterase (AChE) inhibitors are often used to increase the basal acetylcholine level up to a detectable magnitude. This artificial manipulation of the system questions the outcome of pharmacological studies and has led to a large number of experiments pursuing the appropriate physiological and pharmacological concentration of the AChE inhibitors in a range between 0.01 and 100 μM. However, the complexity of the action of these substances, particularly through the involvement of muscarinic autoreceptors and the induction of an autoinhibitory effect on acetylcholine release, did not allow this quest to be resolved completely and suggests the application of advanced mathematical methods for the evaluation of acetylcholine baseline levels. Here we performed a meta-analysis on published datasets of in vivo microdialysis measurements to assess the concentration-dependent effects of various AChE inhibitors on acetylcholine levels within the prefrontal cortex, nucleus accumbens, caudate putamen, and hippocampus in adult rats. In total 3255 rats were analyzed and we found that when compared with the minority of studies (14%) that did not use AChE inhibitors (these studies yielded basal levels between 0.55 and 2.71 nM depending on the brain site) an up to 350-fold increase in baseline values after the application of an inhibitor could be detected. Especially, the derivates neostigmine bromide and physostigmine sulfate seem to produce dramatic effects. Furthermore, concentration-dependent effects after the application of AChE inhibitors could not be established. In the case of neostigmine bromide an inverted concentration (0.1-10 μM)-response relationship was even detected. We conclude that although the presynaptic action of AChE inhibitors is well understood the nonphysiological and concentration-independent augmentation of the acetylcholine system requires the use of a standard protocol in order to produce replicable and comparable results. Our meta-analysis suggests the use of 0.1 μM neostigmine which produces an approximately 10-fold boost of brain baseline levels.

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Section: Resultsmentioning

confidence: 99%

The impact of acetylcholinesterase inhibitors on the extracellular acetylcholine concentrations in the adult rat brain: A meta‐analysis

Noori

Fliegel

Brand

et al. 2012

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“…As regards the effects of EtOH on striatal release of ACh, it has been shown previously by in-vivo microdialysis that EtOH (1 and 2 g/kg), after a short increase, considerably decreased the basal levels of ACh in the medial prefrontal cortex (Jamal et al, 2005), an effect possibly due to a decrease in the activity of choline acetyltransferase (Jamal et al, 2007). Another group also showed an inhibition of basal and stimulated ACh release in the hippocampus in vivo following systemic application of 2.4 g/kg EtOH, whereas local infusion of f10 mM EtOH into the hippocampus led to a stimulation of ACh release (Henn et al, 1998).…”

Section: Ach Release In the Rat Striatummentioning

confidence: 94%

Effects of ethanol and 3,4-methylenedioxymethamphetamine (MDMA) alone or in combination on spontaneous and evoked overflow of dopamine, serotonin and acetylcholine in striatal slices of the rat brain

Riegert¹,

Wedekind²,

Hamida³

et al. 2008

Int. J. Neuropsychopharm.

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Ethanol (EtOH) potentiates the locomotor effects of 3,4-methylenedioxymetamphetamine (MDMA) in rats. This potentiation might involve pharmacokinetic and/or pharmacodynamic mechanisms. We explored whether the latter could be local. Using a slice superfusion approach, we assessed the effects of MDMA (0.3, 3microm) and/or EtOH (2mm) on the spontaneous outflow and electrically evoked release of serotonin (5-HT), dopamine (DA) and acetylcholine (ACh) in the striatum, and for comparison, on 5-HT release in hippocampal and neocortical tissue. MDMA and less effectively EtOH, augmented the outflow of 5-HT in all regions. The electrically evoked 5-HT release was increased by MDMA at 3microm in striatal slices only. With nomifensine throughout, EtOH significantly potentiated the 0.3microm MDMA-induced outflow of 5-HT, but only in striatal slices. EtOH or MDMA also enhanced the spontaneous outflow of DA, but MDMA reduced the electrically evoked DA release. With fluvoxamine throughout superfusion, EtOH potentiated the effect of MDMA on the spontaneous outflow of DA. Finally, 3microm MDMA diminished the electrically evoked release of ACh, an effect involving several receptors (D2, 5-HT2, NMDA, nicotinic, NK1), with some interactions with EtOH. Among other results, we show for the first time a local synergistic interaction of EtOH and MDMA on the spontaneous outflow of striatal DA and 5-HT, which could be relevant to the EtOH-induced potentiation of hyperlocomotion in MDMA-treated rats. These data do not preclude the contribution of other pharmacodynamic and/or pharmacokinetic mechanisms in vivo but support the hypothesis that EtOH may affect the abuse liability of MDMA.

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“…To inhibit aldehyde dehydrogenase (ALDH), animals were administered cyanamide (50 mg/kg i.p.) 60 minutes prior to an acute ethanol injection (2 g/kg, 20% v/v) (Jamal et al., 2005). Saline pretreated animals were used for controls in both experiments.…”

Section: Methodsmentioning

confidence: 99%

Role of Acetaldehyde in Ethanol‐Induced Elevation of the Neuroactive Steroid 3α‐Hydroxy‐5α‐Pregnan‐20‐One in Rats

Boyd¹,

O'Buckley²,

Morrow³

2008

Alcoholism Clin & Exp Res

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Background Systemic ethanol administration increases neuroactive steroid levels that increase ethanol sensitivity. Acetaldehyde is a biologically active compound that may contribute to behavioral and rewarding effects of ethanol. We investigated the role of acetaldehyde in ethanol–induced elevations of 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP) levels in cerebral cortex. Methods Male Sprague-Dawley rats were administered ethanol and plasma acetaldehyde concentrations were measured by gas chromatography to determine relevant concentrations. Rats were then administered acetaldehyde directly, acetaldehyde plus cyanamide to block its degradation, or ethanol in the presence of inhibitors of ethanol metabolism, to determine effects on 3α,5α-THP levels in cerebral cortex. Results Ethanol administration (2 g/kg) to rats results in a peak acetaldehyde concentration of 6-7 μM at 10 minutes that remains stable for the duration of the time points tested. Direct administration of acetaldehyde eliciting this plasma concentration does not increase cerebral cortical 3α,5α-THP levels and inhibition of ethanol-metabolizing enzymes to modify acetaldehyde formation does not alter ethanol–induced 3α,5α-THP levels. However, higher doses of acetaldehyde (75 and 100 mg/kg), in the presence of cyanamide to prevent its metabolism, are capable of increasing cortical 3α,5α-THP levels. Conclusions Physiological concentrations of acetaldehyde are not responsible for ethanol-induced increases in 3α,5α-THP, but a synergistic role for acetaldehyde with ethanol may contribute to increases in 3α,5α-THP levels and ethanol sensitivity.

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Inhibition of acetaldehyde metabolism decreases acetylcholine release in medial frontal cortex of freely moving rats

Cited by 16 publications

References 36 publications

The impact of acetylcholinesterase inhibitors on the extracellular acetylcholine concentrations in the adult rat brain: A meta‐analysis

The impact of acetylcholinesterase inhibitors on the extracellular acetylcholine concentrations in the adult rat brain: A meta‐analysis

Effects of ethanol and 3,4-methylenedioxymethamphetamine (MDMA) alone or in combination on spontaneous and evoked overflow of dopamine, serotonin and acetylcholine in striatal slices of the rat brain

Role of Acetaldehyde in Ethanol‐Induced Elevation of the Neuroactive Steroid 3α‐Hydroxy‐5α‐Pregnan‐20‐One in Rats

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