Effects of serotonin-3 receptor antagonists on the intracranial self-administration of ethanol within the ventral tegmental area of Wistar rats

Abstract

The results of this study suggest that the reinforcing effects of EtOH within the posterior VTA of Wistar rats require activation of local 5-HT(3) receptors.

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

“…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.…”

“…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).…”

“…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.…”

“…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.…”

A Null Mutation of the Serotonin 6 Receptor Alters Acute Responses to Ethanol

“…Some lines of mice carrying a constitutive 5-HT 1B receptor mutation demonstrate increased ethanol consumption compared to wild types (Crabbe et al, 1996;Phillips et al, 1999;however, see Risinger et al, 1999;Bouwknecht et al, 2000;Gorwood et al, 2002 for conflicting reports). Other serotonin receptors, including 5-HT 3 R (Engel et al, 1998;Engel and Allan, 1999;Rodd-Henricks et al, 2003), 5-HT 2A R Maurel et al, 1999;however, see Wilson et al, 2000;Blakley et al, 2001 for conflicting reports), and 5-HT 2C R (Maurel et al, 1999;Tomkins et al, 2002) also modulate ethanol ingestion. Finally, multiple lines of evidence demonstrate that SSRIs affect multiple responses to ethanol ingestion, including overall ethanol ingestion, taste aversion, and ethanol discrimination (Gulley et al, 1995;Gardell et al, 1997;Risinger, 1997;Lamb and Jarbe, 2001).…”