Open field locomotor effects in rats after intraventricular injections of ethanol and the ethanol metabolites acetaldehyde and acetate

Correa, Mercè; Arizzi, Maria N.; Betz, Adrienne J.; Mingote, Susana; Salamone, John D.

doi:10.1016/j.brainresbull.2003.09.013

Cited by 91 publications

(93 citation statements)

References 29 publications

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“…Acetaldehyde infusions into the SNr in the same dose range as ethanol produced a monophasic induction of locomotion, with the maximum effect at 2.8 mmol of acetaldehyde. The present findings are consistent with previous studies showing that intraventricular injections of acetaldehyde can induce locomotor activity (Correa et al, 2003b) and increase responding on a DRL30 operant schedule (Arizzi et al, 2003) over the same dose range as ethanol. It is not clear why acetaldehyde appears to have approximately the same potency as ethanol for inducing locomotion after intracranial injections.…”

Section: Role Of Ethanol Metabolismsupporting

confidence: 93%

“…Peripherally administered acetaldehyde has been shown to decrease motor activity under several conditions . In contrast, acetaldehyde administered into the lateral ventricles was shown to increase locomotor activity (Correa et al, 2003b), and to increase lever pressing rate on a differential reinforcement of low rates 30 s schedule (DRL30), which is an operant paradigm that generates low rates of responding and therefore is sensitive to the stimulant or disinhibiting effects of drugs (Arizzi et al, 2003). Thus, it has been hypothesized that central acetaldehyde can be partially responsible for the motoractivating effects of ethanol.…”

Section: Introductionmentioning

confidence: 99%

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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 Metabolismsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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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“…Quertemont and De Witte (2001) reported that rats showed a dose dependent stimulus preference when ACD was administered peripherally. Much like EtOH, ICV-administered ACD at lower doses, produced an elevation in locomotor activity in rats (Correa et al, 2003), while peripheral and central administration of high doses of ACD produced motor depression in both rats and mice (Durlach et al, 1988;Holtzman & Schneider, 1974;Myers et al, 1987;Quertemont et al, 2004;Tambour et al, 2006). Similar biphasic effects on locomotor activity have been observed following vapor exposure to ACD .…”

Section: Acetaldehyde Is Pharmacologically Active In the Cnsmentioning

confidence: 84%

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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“…Open-field test. The open-field test was used to examine general locomotor activity and is sensitive to the effects of both stimulants and depressants (49). For 3 d before the test session, rats were placed individually in a rectangular test arena [200 mm (height) × 400 mm (width) × 800 mm (length)] made of marine plywood and painted matt black for 20 min to habituate them to the arena and to minimize stress effects.…”

Section: Methodsmentioning

confidence: 99%

Oxytocin prevents ethanol actions at δ subunit-containing GABA _A receptors and attenuates ethanol-induced motor impairment in rats

Bowen

Peters

Absalom

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Even moderate doses of alcohol cause considerable impairment of motor coordination, an effect that substantially involves potentiation of GABAergic activity at δ subunit-containing GABA A receptors (δ-GABA A Rs). Here, we demonstrate that oxytocin selectively attenuates ethanol-induced motor impairment and ethanol-induced increases in GABAergic activity at δ-GABA A Rs and that this effect does not involve the oxytocin receptor. Specifically, oxytocin (1 μg i.c.v.) given before ethanol (1.5 g/kg i.p.) attenuated the sedation and ataxia induced by ethanol in the open-field locomotor test, wire-hanging test, and righting-reflex test in male rats. Using twoelectrode voltage-clamp electrophysiology in Xenopus oocytes, oxytocin was found to completely block ethanol-enhanced activity at α4β1δ and α4β3δ recombinant GABA A Rs. Conversely, ethanol had no effect when applied to α4β1 or α4β3 cells, demonstrating the critical presence of the δ subunit in this effect. Oxytocin had no effect on the motor impairment or in vitro effects induced by the δ-selective GABA A R agonist 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol, which binds at a different site on δ-GABA A Rs than ethanol. Vasopressin, which is a nonapeptide with substantial structural similarity to oxytocin, did not alter ethanol effects at δ-GABA A Rs. This pattern of results confirms the specificity of the interaction between oxytocin and ethanol at δ-GABA A Rs. Finally, our in vitro constructs did not express any oxytocin receptors, meaning that the observed interactions occur directly at δ-GABA A Rs. The profound and direct interaction observed between oxytocin and ethanol at the behavioral and cellular level may have relevance for the development of novel therapeutics for alcohol intoxication and dependence.A receptors (δ-GABA A Rs) play a major role in regulating tonic inhibition in the central nervous system (CNS) (1). The δ-GABA A Rs also represent one of the major targets of ethanol in the CNS, particularly at relatively low ethanol concentrations, and mediate some of the rewarding and ataxic effects of ethanol (2-8). For instance, a genetic polymorphism that exaggerates the actions of ethanol at δ-GABA A Rs also potentiates ethanolinduced motor impairment (2). Further, knockdown of δ subunit expression in the medial shell of the nucleus accumbens reduces alcohol intake in rats (6). Finally, overstimulation and subsequent internalization of α4βδ extrasynaptic GABA A Rs after persistent stimulation by ethanol seem to underlie the development of rapid tolerance to the ataxic effects of ethanol (4).The neuropeptide oxytocin (OT) is well-known for its regulatory role in mammalian sociability and various other central and peripheral physiological processes (9). Early preclinical studies suggested that OT can prevent the development of tolerance to the sedative and ataxic effects of ethanol in rodents (10) and also modulate the severity of ethanol withdrawal (11). More recent studies show that OT reduces alcohol intake in rats (12) and reduces the severity of a...

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Open field locomotor effects in rats after intraventricular injections of ethanol and the ethanol metabolites acetaldehyde and acetate

Cited by 91 publications

References 29 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

Oxytocin prevents ethanol actions at δ subunit-containing GABA _A receptors and attenuates ethanol-induced motor impairment in rats

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Open field locomotor effects in rats after intraventricular injections of ethanol and the ethanol metabolites acetaldehyde and acetate

Cited by 91 publications

References 29 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

Oxytocin prevents ethanol actions at δ subunit-containing GABA A receptors and attenuates ethanol-induced motor impairment in rats

Contact Info

Product

Resources

About

Oxytocin prevents ethanol actions at δ subunit-containing GABA _A receptors and attenuates ethanol-induced motor impairment in rats