Ethanol Directly Excites Dopaminergic Ventral Tegmental Area Reward Neurons

Brodie, Mark S.; Pesold, Christine; Appel, Sarah B.

doi:10.1111/j.1530-0277.1999.tb04082.x

Cited by 348 publications

(169 citation statements)

References 26 publications

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“…EtOH excitation in dopaminergic neurons of the rat has been shown to be blocked by quinidine, but not by blockers of h-current (Appel et al, 2003). Furthermore, EtOH excites individual VTA neurons dissociated from brain slices (Brodie et al, 1999;Ye et al, 2001), a preparation that would be expected to reduce the ability of synthesized ACD to act on these independent VTA neurons, and the concentration-response for EtOH excitation of dissociated dopaminergic VTA neurons (Brodie et al, 1999) is similar to that observed in brain slices (Brodie et al, 1990).…”

Section: Differences Between Acetaldehyde and Alcohol: Electrophysiolmentioning

confidence: 64%

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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Section: Differences Between Acetaldehyde and Alcohol: Electrophysiolmentioning

confidence: 64%

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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“…At the systems level, the increased release of DA associated with the administration of toluene and the CNS-depressant EtOH has been temporally associated in vivo with an increase in the number of impulses originating within the VTA, the site of origin of the mesolimbic DA pathway (Gessa et al, 1985;Riegel and French, 1999a, b). At the cellular level both substances stimulate DA neuronal activityFan effect that has been attributed to disinhibitory mechanisms as well as the direct activation of VTA DA neurons (Brodie et al, 1990(Brodie et al, , 1999. Taken together, these noticeable similarities would appear to support the general conclusions that the abused inhalant toluene may trigger the release of DA in the NAC via impulse-dependent mechanisms initiated upstream at the level of the cell bodies in the VTA.…”

Section: -Ohda Studies and Toluenementioning

confidence: 71%

Toluene-Induced Locomotor Activity is Blocked by 6-Hydroxydopamine Lesions of the Nucleus Accumbens and the mGluR2/3 Agonist LY379268

Riegel

Ali

French

2003

Neuropsychopharmacol

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The abuse of volatile inhalants remains a prominent, yet poorly understood, form of substance abuse among youth. Nevertheless, the identification of a mechanism underlying the reinforcing properties of inhalants has been hampered by the lack of a clearly identifiable neural substrate upon which these chemicals act. One ingredient that is common to many abused inhalants is toluene, an organic solvent that is self-administered by nonhuman primates and rodents. Most drugs of abuse have been found to elicit forward locomotion in rats, an effect owing to the activation of mesoaccumbal dopamine (DA) pathways. Thus, the present study was undertaken using two different approaches to determine whether toluene-induced locomotor hyperactivity is also ultimately dependent upon DA neurotransmission in the mesolimbic nucleus accumbens (NAC). Here we report on the effects of 6-hydroxydopamine (6-OHDA) lesions of the NAC or pretreatment with the metabotropic mGlu2/3 receptor agonist LY379268 on toluene-induced locomotor activity. Both procedures, which are known to alter neurotransmission within the NAC, significantly attenuated toluene's locomotor stimulatory effects. These results provide strong support for a central mechanism of action of inhalants, which in the past has been more typically attributed to general nonspecific mechanisms throughout the brain. Moreover, as with other drugs of abuse, the NAC may be the final common pathway subserving toluene's abuse liability.

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“…In addition, the dopaminergic system has also been strongly implicated in alcohol abuse, particularly in mediating its acute reinforcing properties. Acute alcohol exposure can enhance the firing rate of dopaminergic cells in both the ventral tegmental area (VTA) (Brodie et al, 1999) and the substantia nigra (Mereu et al, 1984). This is thought to correspond to an increase in dopamine release in a number of brain regions, including the nucleus accumbens (Melendez et al, 2002;Gonzales et al, 2004), striatum (Melendez et al, 2003), the central nucleus of the amygdala (Yoshimoto et al, 2000) and the bed nucleus of the stria terminalis (BNST) (Carboni et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Chronic ethanol exposure leads to divergent control of dopaminergic synapses in distinct target regions

Healey

Winder

Kash

2008

Alcohol

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Neuroadaptations following chronic exposure to alcohol are hypothesized to play important roles in alcohol-induced alterations in behavior, in particular increased alcohol drinking and anxiety like behavior. Dopaminergic signaling plays a key role in reward-related behavior, with evidence suggesting it undergoes modification following exposure to drugs of abuse. A large literature indicates an involvement of dopaminergic signaling in response to alcohol. Using a chronic inhalation model of ethanol exposure in mice, we have begun to investigate the effects of alcohol intake on dopaminergic signaling by examining protein levels of tyrosine hydroxylase (TH) and the dopamine transporter (DAT), as well as monoamine metabolites in three different target fields of three different dopaminergic nuclei. We have focused on the dorsal lateral bed nucleus of the stria terminalis (dBNST) because of the reported involvement of dBNST dopamine in ethanol intake, and the nucleus accumbens (NAc) and dorsal striatum because of their dense dopaminergic innervation. After either a chronic intermittent exposure (CIE) or continuous exposure (CCE) regimen, mice were killed, and tissue punches collected from the dBNST, NAc and striatum for Western analysis. Strikingly, we found divergent regulation of TH and DAT protein levels across these three regions that was dependent upon the means of exposure. These data thus suggest that distinct populations of catecholamine neurons may be differentially regulated by ethanol, and that ethanol and withdrawal interact to produce differential adaptations in these systems.

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Ethanol Directly Excites Dopaminergic Ventral Tegmental Area Reward Neurons

Abstract: These data provide strong evidence that ethanol directly excites dopaminergic VTA neurons, as this excitation still occurs in the absence of input from surrounding neurons.

Cited by 348 publications

References 26 publications

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

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

Toluene-Induced Locomotor Activity is Blocked by 6-Hydroxydopamine Lesions of the Nucleus Accumbens and the mGluR2/3 Agonist LY379268

Chronic ethanol exposure leads to divergent control of dopaminergic synapses in distinct target regions

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