The mesolimbic dopamine system is involved in the rewarding 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 determine (1) if the posterior ventral tegmental area (p-VTA) mediates EtOH-seeking, (2) if microinjections of EtOH into the p-VTA could stimulate EtOH-seeking, and (3) the involvement of p-VTA dopamine (DA) neurons in EtOH-seeking. Method: Alcohol-Preferring (P) rats were trained to self-administer 15% ethanol (EtOH) and water. After 10 weeks, rats underwent extinction training, followed by a 2 week homecage period. During the homecage period, rats were then bilaterally implanted with guide cannulae aimed at the p-VTA or anterior VTA (a-VTA). EtOH-seeking was assessed by the Pavlovian Spontaneous Recovery (PSR) model. Separate experiments examined the effects of; 1) microinjection of quinpirole into the p- VTA, 2) EtOH microinjected into the p-VTA, 3) co-administration of EtOH and quinpirole into the p-VTA, 4) microinjection of quinpirole into the anterior VTA (a-VTA), and 5) microinjection of EtOH into the a-VTA. Quinpirole microinjected into the p-VTA reduced EtOH-seeking. Microinjections of EtOH into the p-VTA increased EtOH-seeking. Pretreatment with both quinpirole and EtOH into the p-VTA reduced EtOH-seeking. Microinjections of quinpirole or EtOH into the a-VTA did not alter EtOH-seeking. Overall, the results suggest that the p-VTA is a neuroanatomical substrate mediating alcohol-seeking behavior and that activation of local DA neurons is involved.
- Alcohol-Preferring (P) rats
- Ethanol-Seeking Behavior
- Pavlovian Spontaneous Recovery
- Ventral Tegmental Area
- Received March 29, 2010.
- Revision received December 7, 2010.
- Accepted December 7, 2010.
- The American Society for Pharmacology and Experimental Therapeutics