Intraventricular self-administration of acetaldehyde and voluntary consumption of ethanol in rats

Brown, Zavie W.; Amit, Zalman; Smith, Brian R.

doi:10.1016/s0163-1047(80)91487-9

Cited by 71 publications

(34 citation statements)

References 9 publications

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“…The notion that ethanol metabolism in the brain is important for some of the behavioral effects of ethanol is supported by the reports that manipulations of catalase activity exert a powerful effect on ethanol-induced behavior (Aragon et al, 1992a;Aragon and Amit, 1993;Correa et al, 1999aCorrea et al, , b, 2000Correa et al, , 2001Correa et al, , 2004aSanchis-Segura et al, 1999a-c;Pastor et al, 2002). Additional support is provided by studies showing behavioral effects of acetaldehyde after central administration (Myers and Veale, 1969;Brown et al, 1978Brown et al, , 1979Brown et al, , 1980Smith et al, 1984;Arizzi et al, 2003;Correa et al, 2003b, c;Rodd-Henricks et al, 2002;Rodd et al, 2005). The central administration of acetaldehyde avoids the issue of brain penetrability, and therefore more directly assesses the effects of central acetaldehyde on distinct aspects of behavior.…”

Section: Role Of Ethanol Metabolismmentioning

confidence: 92%

Motor Stimulant Effects of Ethanol Injected into the Substantia Nigra Pars Reticulata: Importance of Catalase-Mediated Metabolism and the Role of Acetaldehyde

Arizzi-LaFrance

Correa

Aragón

et al. 2005

Neuropsychopharmacol

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A series of experiments was conducted to investigate the locomotor effects of local injections of ethanol and the ethanol metabolite, acetaldehyde, into substantia nigra pars reticulata (SNr). Infusions of ethanol into SNr resulted in a dose-related increase in locomotor activity, with maximal effects at a dose of 1.4 mmol. Ethanol injected into a control site dorsal to substantia nigra failed to stimulate locomotion, and another inactive site was identified in brainstem areas posterior to substantia nigra. The locomotor effects of intranigral ethanol (1.4 mmol) were reduced by coadministration of 10 mg/kg sodium azide, a catalase inhibitor that acts to reduce the metabolism of ethanol into acetaldehyde in the brain. SNr infusions of acetaldehyde, which is the first metabolite of ethanol, also increased locomotion. Taken together, these results indicate that SNr is one of the sites at which ethanol and acetaldehyde may be acting to induce locomotor activity. These results are consistent with the hypothesis that acetaldehyde is a centrally active metabolite of ethanol, and provide further support for the idea that catalase activity is a critical step in the regulation of ethanol-induced motor activity. These studies have implications for understanding the brain mechanisms involved in mediating the ascending limb of the biphasic dose-response curve for the effect of ethanol on locomotor activity.

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Section: Role Of Ethanol Metabolismmentioning

confidence: 92%

Motor Stimulant Effects of Ethanol Injected into the Substantia Nigra Pars Reticulata: Importance of Catalase-Mediated Metabolism and the Role of Acetaldehyde

Arizzi-LaFrance

Correa

Aragón

et al. 2005

Neuropsychopharmacol

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“…It was also discovered that ACD possessed reinforcing properties as rats would readily self-administer ACD through both ICV (Amit et al, 1977;Brown et al, 1979;Brown et al, 1980) and intra-venous (IV; Myers et al, 1984) routes. Animals receiving ICV infusions of ACD exhibited a conditioned place preference (CPP) associated with the drug (Smith et al, 1984) while peripheral injections of ACD induced a conditioned taste aversion similar to alcohol (Aragon et al, 1986).…”

Section: Acetaldehyde Is Pharmacologically Active In the Cnsmentioning

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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“…Accordingly, acetaldehyde is readily self-administered intravenously (i.v.) (Myers et al, 1982(Myers et al, , 1984, directly into the VTA (RoddHenricks et al, 2002) and into the cerebral ventricles (Brown et al, 1979(Brown et al, , 1980. Further, when administered intracerebroventricularly, acetaldehyde is able to induce place preference in rats (Smith et al, 1984) and to produce a conditioned stimulus preference, even when administered peripherally (Quertemont and De Witte, 2001).…”

Section: Introductionmentioning

confidence: 99%

Acetaldehyde Increases Dopaminergic Neuronal Activity in the VTA

Foddai

Dosia

Spiga

et al. 2003

Neuropsychopharmacol

156

137

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Acetaldehyde is the first and principal metabolite of ethanol administered systemically. To its rise in blood, after administration of disulfiram, is ascribed the aversive reaction that should discourage alcoholics from drinking. In the present study, we sought to determine the effect of acetaldehyde on the electrophysiological properties of dopamine (DA)-containing neurons in the ventro tegmental area (VTA) of rats in vivo. Intravenous (i.v.) administration of acetaldehyde (5-40 mg/kg) readily and dose-dependently increased the firing rate, spikes/burst, and burst firing of VTA neurons. Ethanol (250-1000 mg/kg/i.v.) administration produced similar increments in electrophysiological parameters. In addition, a second group of rats was pretreated with the alcohol-dehydrogenase inhibitor 4-methylpyrazole (90 mg/kg) intraperitoneally (i.p.), and ethanol and acetaldehyde were administered i.v. at the same doses, 48 h later. In this group, ethanol effects were drastically reduced and the firing rate, spikes/burst, and burst firing were not significantly altered. In contrast, acetaldehyde fully retained its capacity to stimulate electrophysiological indices. The results indicate that acetaldehyde produces electrophysiological actions on VTA neurons in vivo, similar to those produced by ethanol, and significantly participate in ethanol-induced increment in DA neuronal activity. These results also suggest that acetaldehyde, by increasing DA neuronal activity in the VTA, may significantly contribute to the centrally mediated positive motivational properties of ethanol, which would oppose the well-known peripherally originating aversive properties.

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Intraventricular self-administration of acetaldehyde and voluntary consumption of ethanol in rats

Cited by 71 publications

References 9 publications

Motor Stimulant Effects of Ethanol Injected into the Substantia Nigra Pars Reticulata: Importance of Catalase-Mediated Metabolism and the Role of Acetaldehyde

Motor Stimulant Effects of Ethanol Injected into the Substantia Nigra Pars Reticulata: Importance of Catalase-Mediated Metabolism and the Role of Acetaldehyde

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

Acetaldehyde Increases Dopaminergic Neuronal Activity in the VTA

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