Low doses of ethanol activate dopaminergic neurons in the ventral tegmental area

Gessa, Gian Luigi; Muntoni, F.; Collu, Maria; Vargiu, L; Mereu, Giampaolo

doi:10.1016/0006-8993(85)90381-6

Cited by 727 publications

(356 citation statements)

References 23 publications

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“…The mechanism underlying the excitatory effects of ethanol is unknown. Still, there is evidence that low doses of ethanol increase the firing rate of dopam inergic cells in the ventral tegmental area (Gessa et al 1985) and enhance the release of dopam ine in the nucleus accumbens (Di Chiara and Im perato 1985). Since such enhanced dopaminergic activity produces an increase in loco m otor activity (Pijnenburg and van Rossum 1973;Pijnenburg et al 1975), it is reasonable to suggest that this mechanism gave rise to the excitatory effects seen in HR.…”

Section: Discussionmentioning

confidence: 99%

“…C h iara and Imperato 1985; see also : Gessa et al 1985;Y oshim oto et al 1991), and an increased release of p lasm a corticosteroids (stress : Ellis 1966;ethanol: Patel andPohorecky 1988,1989;Spencer and McEwen 1990). Apart from the above-mentioned differences in responsiveness of the central catecholaminergic sys tems, H R and LR are also known to show differential responses to stress: both stress-induced behavioural responses and stress-induced neurochemical responses such as the increase in plasma corticosteroids are much greater in HR than in LR (Cools et al 1990;Rots et aL 1995).…”

Section: A Pparatusmentioning

confidence: 99%

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Analysis of the biphasic locomotor response to ethanol in high and low responders to novelty: a study in nijmegen wistar rats

Gingras

Cools

1996

Psychopharmacology

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The aim of the study was to investigate the biphasic locom otor response to ethanol in rats. Based on the recent finding that high responders to novelty (HR) and low responders to novelty (LR), selected from an outbred Nijmegen W istar rat population, show differences in ethanol intake and preference, it was ini tially investigated to what extent H R and L R differ in their locom otor response to ethanol, A dose-response curve (0.2-2.0 g/kg, IP) was established using stan dardized activity boxes. H R showed a significant increase at 0.5 g/kg, followed by a significant decrease at doses 1.0-2.0 g/kg; LR showed only a decrease at doses 1.0-2.0 g/kg. Secondly, it was investigated to what extent stress altered the ethanol-induced increase and decrease, respectively. For that purpose, the ethanol-induced locom otor effects (0.5 and 1.0 g/kg) were analyzed in habituated and noil-habituated (stressed) H R and LR; habituation consisted of a 15-min adaptation period to the activity cages. Stress significantly enhanced the excitatory effects in H R , but had no effect on the sedative effects in H R and LR. Finally, the locom otor effects of sub-chronic treatm ent (7 days) with an excitatory (0.5 g/kg) or sedative (LO g/kg) dose were analyzed in H R and LR. The excitatory effect of 0.5 g /k g disappeared throughout the treatm ent in H R , whereas the sedative effects of 1.0 g/kg remained the same in H R and LR. It is con cluded that the mechanism underlying the ethanolinduced m otor excitation differs completely from that underlying the ethanol-induced sedation. Given the known differences in the m ake-up of the brain and endocrine system between H R and LR, these animals are suggested to be good models for studying the m ech anisms underlying the biphasic locom otor response to ethanol in rats.

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Section: Discussionmentioning

confidence: 99%

Section: A Pparatusmentioning

confidence: 99%

Analysis of the biphasic locomotor response to ethanol in high and low responders to novelty: a study in nijmegen wistar rats

Gingras

Cools

1996

Psychopharmacology

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“…The administration of these substances in rats has been shown to stimulate DA release (DiChiara and Imperato, 1988;Yim et al, 1998Yim et al, , 2002. 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.…”

Section: -Ohda Studies and Toluenementioning

confidence: 99%

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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“…Accordingly, acute ethanol administration increases the electrophysiological activity of these neurons in vivo (Gessa et al, 1985) and in vitro (Brodie et al, 1990), and augments DA microdialysate concentrations in terminal areas (Imperato and Di Chiara, 1986) of freely behaving rats. Conversely, ethanol withdrawal decreases dopaminergic neuronal activity in rats in vivo (Diana et al, 1993) and mice in vitro (Bailey et al, 1998), and reduces DA extracellular concentrations in the nucleus accumbens (Rossetti et al, 1992;Diana et al, 1993;Weiss et al, 1996).…”

Section: Introductionmentioning

confidence: 95%

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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Low doses of ethanol activate dopaminergic neurons in the ventral tegmental area

Cited by 727 publications

References 23 publications

Analysis of the biphasic locomotor response to ethanol in high and low responders to novelty: a study in nijmegen wistar rats

Analysis of the biphasic locomotor response to ethanol in high and low responders to novelty: a study in nijmegen wistar rats

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

Acetaldehyde Increases Dopaminergic Neuronal Activity in the VTA

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