The Posterior Ventral Tegmental Area Mediates Alcohol-Seeking Behavior in Alcohol-Preferring Rats

The mesolimbic dopamine (DA) system is involved in the re-warding process of drugs of abuse and is activated during the anticipation of drug availability. However, the neurocircuitry that regulates ethanol (EtOH)-seeking has not been adequately investigated. The objectives of the present study were to de-termine 1) whether the posterior ventral tegmental area (p-VTA) mediates EtOH-seeking, 2) whether microinjections of EtOH into the p-VTA could stimulate EtOH-seeking, and (3) the in-volvement of p-VTA DA neurons in EtOH-seeking. Alcohol-preferring rats were trained to self-administer 15 % EtOH and water. After 10 weeks, rats underwent extinction training, fol-lowed by 2 weeks in their home cages. During the home-cage period, rats were then bilaterally implanted with guide cannulae aimed at the p-VTA or anterior ventral tegmental area (a-VTA). EtOH-seeking was assessed by the Pavlovian spontaneous recovery model. Separate experiments examined the effects of: 1) microinjection of quinpirole into the p-VTA, 2) EtOH micro-injected into the p-VTA, 3) coadministration of EtOH and quin-pirole into the p-VTA, 4) microinjection of quinpirole into the a-VTA, and 5) microinjection of EtOH into the a-VTA. Quinpirole microinjected into the p-VTA reduced EtOH-seeking. Microin-jections of EtOH into the p-VTA increased EtOH-seeking. Pre-treatment with both quinpirole and EtOH into the p-VTA re-duced EtOH-seeking. Microinjections of quinpirole or EtOH into the a-VTA did not alter EtOH-seeking. Overall, the results sug-gest that the p-VTA is a neuroanatomical substrate mediating alcohol-seeking behavior and that activation of local DA neu-rons is involved