1. ¹Department of Psychiatry, Institute of Psychiatric Research, Indiana University-Purdue University at Indianapolis, Indianapolis, IN, USA
2. ²Department of Biochemistry, Indiana University School of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, IN, USA
3. ³Department of Psychology, Purdue School of Science, Indiana University-Purdue University at Indianapolis, Indianapolis, IN, USA
4. ⁴Stanford University, Stanford, CA, USA
5. ⁵Technofyn Associates, Palo Alto, CA, USA
6. ⁶NIAAA, Bethesda, MD, USA

Correspondence: Dr ZA Rodd, Indiana University School of Medicine, Institute of Psychiatric Research, 791 Union Drive, Indianapolis, IN 46202-4887, USA. Tel: +1 317 278 3003; Fax: +1 317 274 1365; E-mail: zrodd@iupui.edu

Received 4 March 2004; Revised 27 July 2004; Accepted 5 August 2004; Published online 22 September 2004.

Abstract

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-HT₃) 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 M 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 M) blocked the self-infusions of 150 mg% EtOH and 23 M ACD into the posterior VTA; and (d) coadministration of 200 M ICS205,930 (5-HT₃ receptor antagonist) prevented the self-infusion of 150 mg% EtOH, whereas concentrations of ICS 205,930 up to 400 M had no effect on the self-infusion of 23 M 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-HT₃ receptors within the posterior VTA is involved in the self-infusion of EtOH, but not ACD.