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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Smoking involves heating a drug to form a mixture of drug vapor and gaseous degradation products. These gases subsequently cool and condense into aerosol particles that are inhaled. Here, we demonstrate rapid and reliable systemic delivery of pure pharmaceutical compounds without degradation products through a related process that also involves inhalation of thermally generated aerosol. Drug is coated as a thin film on a metallic substrate and vaporized by heating the metal. The thin nature of the drug coating minimizes the length of time during which the drug is exposed to elevated temperatures, thereby preventing its thermal decomposition. The vaporized, gas-phase drug rapidly condenses and coagulates into micrometer-sized aerosol particles. For the commonly prescribed antimigraine drug rizatriptan, inhalation of these particles results in nearly instantaneous systemic drug action.

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This article represents the proceedings of a symposium at the 2004 annual meeting of the Research Society on Alcoholism in Vancouver, Canada. The symposium was organized by Etienne Quertemont and chaired by Kathleen A. Grant. The presentations were (1) Behavioral stimulant effects of intracranial injections of ethanol and acetaldehyde in rats, by Mercè Correa, Maria N. Arizzi and John D. Salamone; (2) Behavioral characterization of acetaldehyde in mice, by Etienne Quertemont and Sophie Tambour; (3) Role of brain catalase and central formed acetaldehyde in ethanol's behavioral effects, by Carlos M.G. Aragon; (4) Contrasting the reinforcing actions of acetaldehyde and ethanol within the ventral tegmental area (VTA) of alcohol-preferring (P) rats, by William J. McBride, Zachary A. Rodd, Avram Goldstein, Alejandro Zaffaroni and Ting-Kai Li; and (5) Acetaldehyde increases dopaminergic transmission in the limbic system, by Milena Pisano and Marco Diana.