Intracranial Self-Administration of Ethanol within the Ventral Tegmental Area of Male Wistar Rats: Evidence for Involvement of Dopamine Neurons

Rodd, Zachary A.; Meléndez, Roberto I.; Bell, Richard L.; Kuc, Kelly A.; Zhang, Ying; Murphy, James M.; McBride, William J.

doi:10.1523/jneurosci.1319-03.2004

Cited by 182 publications

(211 citation statements)

References 40 publications

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“…Although not systematically studied, the estrous cycle did not appear to significantly alter self-administration behavior, as indicated by fairly stable responding across several sessions, when the same concentration of EtOH (RoddHenricks et al, 2003) or ACD (Rodd-Henricks et al, 2002b) was given. Furthermore, a significant gender effect for the self-infusion of EtOH was not observed in a recent study using male Wistar rats (Rodd et al, 2004b).…”

Section: Animalsmentioning

confidence: 71%

“…Local administration of triazole as opposed to peripheral injection was used for a combination of reasons. Our previous success with coinfusing quinpirole (Rodd et al, 2004b) or 5-HT 3 antagonists (Rodd-Henricks et al, 2003) suggested that a local pharmacological effect for blocking the actions of EtOH could be obtained with this approach. Triazole is an irreversible inhibitor (reviewed in Hunt, 1996;Smith et al, 1997) and should produce progressive inhibition of intracellular catalase activity around the injection site during each of the 4-h sessions.…”

Section: General Test Conditionmentioning

confidence: 99%

“…Previous studies indicated that Wistar rats selfadministered 150-250 mg% EtOH directly into the posterior ventral tegmental area (VTA), whereas these concentrations were not self-infused into the anterior VTA (Rodd-Henricks et al, 2000). Furthermore, the intracranial self-administration (ICSA) of EtOH into the posterior VTA of Wistar rats was blocked with coinfusion of serotonin-3 (5-HT 3 ) receptor antagonists (Rodd-Henricks et al, 2003) or the DA D 2,3 agonist quinpirole (Rodd et al, 2004b), suggesting the involvement of local 5-HT 3 receptors and VTA-DA neurons in the reinforcing effects of EtOH. In a subsequent study, the ICSA of EtOH into the posterior VTA was compared between alcohol-preferring (P) and Wistar rats (Rodd et al, 2004a).…”

Section: Introductionmentioning

confidence: 99%

“…However, the anteriorposterior subregional heterogeneity for the reinforcing effects of EtOH was not examined in the P rat. In addition, pharmacological studies to determine the involvement of D 2 and 5-HT 3 receptors in mediating EtOH self-infusions, similar to those conducted with Wistar rats (Rodd et al, 2004b;Rodd-Henricks et al, 2003), have not been undertaken with P rats.…”

Section: Introductionmentioning

confidence: 99%

“…A second experiment attempted to reduce the formation of ACD from EtOH by coadministering 3-amino-1,2,4-triazole (triazole), a catalase inhibitor (Cohen et al, 1980;Koechling and Amit, 1994), and examined the effects on the selfinfusion of EtOH into the posterior VTA. Additional experiments examined whether the reinforcing effects of ACD within the VTA are mediated by mechanisms similar to those supporting the reinforcing effects of EtOH, that is, did ACD self-infusion also require activation of VTA DA neurons and local 5-HT 3 receptors (Rodd et al, 2004b;Rodd-Henricks et al, 2003). If the formation of ACD underlied the reinforcing effects of EtOH within the VTA, then ACD self-infusion should be regulated in a manner similar to that for EtOH.…”

Section: Introductionmentioning

confidence: 99%

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Regional Heterogeneity for the Intracranial Self-Administration of Ethanol and Acetaldehyde within the Ventral Tegmental Area of Alcohol-Preferring (P) Rats: Involvement of Dopamine and Serotonin

Rodd

Bell

Zhang

et al. 2004

Neuropsychopharmacol

139

175

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The meso-limbic dopamine (DA) system has an important role in regulating alcohol drinking. Previous findings from our laboratory indicated that Wistar rats self-administered ethanol (EtOH) directly into the posterior, but not anterior, ventral tegmental area (VTA), and that coadministration of a DA D 2,3 receptor agonist or a serotonin-3 (5-HT 3 ) receptor antagonist blocked EtOH self-administration. In addition, we reported that alcohol-preferring (P) rats self-administered acetaldehyde (ACD), the first metabolite of EtOH, into the posterior VTA. The objectives of this study were to compare the reinforcing effects of EtOH and ACD within the VTA of P rats to examine the possibility that the reinforcing effects of EtOH within the VTA may be mediated by its conversion to ACD. Adult female P rats were stereotaxically implanted with guide cannulae aimed at either the posterior or anterior VTA. At 1 week after surgery, rats were placed in standard two-lever (active and inactive) experimental chambers for a total of seven to eight sessions. The 4-h sessions were conducted every other day. The results indicated that (a) 75-300 mg% (17-66 mM) EtOH and 6-90 mM ACD were self-administered into the posterior, but not anterior, VTA; (b) the self-administration of 150 mg% EtOH was not altered by coinfusion of a catalase inhibitor; (c) coadministration of the D 2/3 agonist quinpirole (100 mM) blocked the self-infusions of 150 mg% EtOH and 23 mM ACD into the posterior VTA; and (d) coadministration of 200 mM ICS205,930 (5-HT 3 receptor antagonist) prevented the self-infusion of 150 mg% EtOH, whereas concentrations of ICS 205,930 up to 400 mM had no effect on the self-infusion of 23 mM ACD into the posterior VTA. Overall, the results of this study indicate that EtOH and ACD can independently produce reinforcing effects within the posterior VTA, and that activation of DA neurons mediates these effects. Furthermore, activation of 5-HT 3 receptors within the posterior VTA is involved in the self-infusion of EtOH, but not ACD.

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Section: Animalsmentioning

confidence: 71%

Section: General Test Conditionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regional Heterogeneity for the Intracranial Self-Administration of Ethanol and Acetaldehyde within the Ventral Tegmental Area of Alcohol-Preferring (P) Rats: Involvement of Dopamine and Serotonin

Rodd

Bell

Zhang

et al. 2004

Neuropsychopharmacol

139

175

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Dopamine Receptors: Neurotherapeutic Targets for Substance Use Disorders

Nilson¹,

Felsing²,

Allen³

2022

GPCRs as Therapeutic Targets

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Afferents of the ventral tegmental area in the rat-anatomical substratum for integrative functions

2005

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The ventral tegmental area (VTA) is critically important to an organism's capacity to detect rewards and novelty and to enlist appropriate behavioral responses. Although there has been substantial progress concerning information processing at the single cell and molecular levels in the VTA, our knowledge of its overall afferent connections is based principally on the benchmark description by Phillipson ([1979] J. Comp. Neurol. 187:117-144). Given that, since then, the sensitivity of tracing methods and knowledge about the organization of brain structures have increased considerably, we undertook to reevaluate the VTA afferents of the rat. The retrograde tracer Fluoro-Gold was injected into different parts of the VTA, and labeled neurons were visualized by immunocytochemistry. Retrogradely labeled neurons were not confined to nuclei but rather constituted an elongated formation stretching from the prefrontal cortex rostrally to the medulla oblongata caudally. In the case of descending afferents, this formation was centered on the medial forebrain bundle and the fasciculus retroflexus. The input to the VTA in general was bilateral, with a smaller descending and comparable ascending projection from the contralateral side. Injections of the anterograde tracers Phaseolus vulgaris-leucoagglutinin or biotinylated dextran amine into selected forebrain structures revealed a surprisingly sparse terminal arborization in the VTA. Furthermore, structures projecting to the VTA innervate other brain areas with similar or greater robustness, which in turn also provide a strong input to the VTA, indicating an anatomical network. Given the importance of the VTA in basic behaviors, this organization might provide a basis for an extraordinary level of afferent integration.

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Intracranial Self-Administration of Ethanol within the Ventral Tegmental Area of Male Wistar Rats: Evidence for Involvement of Dopamine Neurons

Cited by 182 publications

References 40 publications

Regional Heterogeneity for the Intracranial Self-Administration of Ethanol and Acetaldehyde within the Ventral Tegmental Area of Alcohol-Preferring (P) Rats: Involvement of Dopamine and Serotonin

Regional Heterogeneity for the Intracranial Self-Administration of Ethanol and Acetaldehyde within the Ventral Tegmental Area of Alcohol-Preferring (P) Rats: Involvement of Dopamine and Serotonin

Dopamine Receptors: Neurotherapeutic Targets for Substance Use Disorders

Afferents of the ventral tegmental area in the rat-anatomical substratum for integrative functions

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