Intracranial self-administration of ethanol within the ventral tegmental area of male Wistar rats: evidence for involvement of dopamine neurons

Abstract

Previous work from our laboratory indicated that female Wistar rats will self-administer ethanol (EtOH) directly into the posterior ventral tegmental area (VTA). These results suggested that VTA dopamine (DA) neurons might be involved in mediating the reinforcing actions of EtOH within this region. The objectives of this study were to determine (1) the dose-response effects for the self-administration of EtOH into the VTA of male Wistar rats, and (2) the involvement of VTA DA neurons in the reinforcing actions of EtOH within the VTA. Adult male Wistar rats were implanted stereotaxically with guide cannulas aimed at the posterior or anterior VTA. After 1 week, rats were placed in standard two-lever (active and inactive) experimental chambers for a total of seven to eight sessions. The first experiment determined the intracranial self-administration of EtOH (0-400 mg%) into the posterior and anterior VTA. The second experiment examined the effects of coadministration of the D2/3 agonist quinpirole on the acquisition and maintenance of EtOH self-infusions into the posterior VTA. The final experiment determined the effects of a D2 antagonist (sulpiride) to reinstate self-administration behavior in rats given EtOH and quinpirole to coadminister. Male Wistar rats self-infused 100-300 mg% EtOH directly into the posterior, but not anterior, VTA. Coadministration of quinpirole prevented the acquisition and extinguished the maintenance of EtOH self-infusion into the posterior VTA, and addition of sulpiride reinstated EtOH self-administration. The results of this study indicate that EtOH is reinforcing within the posterior VTA of male Wistar rats and suggest that activation of VTA DA neurons is involved in this process.

Figure 1.

Illustration depicts the injection sites in the anterior and posterior VTA, sites outside of the VTA, of male Wistar rats self-administering various concentrations of EtOH. Closed circles represent placements of injection sites within the posterior VTA (defined as –5.4 to –6.0 mm bregma), closed squares represent placements of injection sites in the anterior VTA (defined as –4.8 to –5.3 mm bregma), and open squares represent injection placements outside the VTA.

Figure 2.

Dose–response graph for the number of infusions averaged over the first four sessions for the self-infusion of 100–400 mg% EtOH into non-VTA sites (a); 0, 75, 100, 150, 200, 250, 300, and 400 mg% EtOH into the posterior VTA (b); and 0, 100, 200, 300, or 400 mg% EtOH into the anterior VTA of male Wistar rats (c). The asterisks indicate that the number of infusions administered is significantly greater (p < 0.05) than aCSF. Data are the means ± SEM; for non-VTA sites, n = 6; for posterior VTA, n = 6–8/dose; and for anterior VTA, n = 6–7/dose.

Figure 3.

Responses on the active and inactive lever by male Wistar rats for the self-infusion of aCSF for seven consecutive sessions, or 75 or 100 mg% EtOH directly into the posterior VTA for the first four sessions (acquisition), aCSF for sessions 5 and 6 (extinction), and EtOH again in session 7 (reinstatement). The asterisks indicate responses on the active lever were significantly higher (p < 0.05) than responses on the inactive lever for that session. Data are the means ± SEM; n = 6–8/group.

Figure 4.

Responses on the active and inactive lever by male Wistar rats for the self-infusion of 150, 250, or 300 mg% EtOH directly into the posterior VTA for the first four sessions (acquisition), aCSF for sessions 5 and 6 (extinction), and EtOH again in session 7 (reinstatement). The asterisks indicate responses on the active lever were significantly higher (p < 0.05) than responses on the inactive lever for that session. Data are the means ± SEM; n = 6–8/group.

Figure 6.

Responses on the active and inactive lever by male Wistar rats for the self-infusion of 200 mg% EtOH for seven consecutive sessions (a, top); 200 mg% EtOH for the first four sessions and 200 mg% EtOH plus 1 or 10μm quinpirole (Quin) in sessions 5 and 6 (b, middle and bottom); and 200 mg% EtOH again in session seven directly into the posterior VTA (c). The asterisks indicate responses on the active lever were significantly higher (p < 0.05) than responses on the inactive lever for that session. Data are the means ± SEM; n = 6–8/group.

Figure 5.

Averaged number of infusions over seven sessions for the self-infusion of aCSF, 100 μm quinpirole (Q), 200 mg% ethanol (E), and 200 mg% E plus 1, 10, or 100 μm Q into the posterior VTA. The asterisks indicate that the number of infusions administered is significantly greater (p < 0.05) than aCSF. Data are the means ± SEM; n = 3–5/group.

Figure 7.

Responses on the active and inactive lever by male Wistar rats for the self-infusion of 200 mg% EtOH for the first four sessions, 200 mg% EtOH plus 100 μm quinpirole (Quin) in sessions 5 and 6, and 200 mg% EtOH plus 100 μm Quin and 10 or 100 μm sulpiride (Sulp) in sessions 7 and 8 directly into the posterior VTA. The asterisks indicate responses on the active lever were significantly higher (p < 0.05) than responses on the inactive lever for that session. The # indicates that responses on the active lever were significantly higher than inactive lever responses in that session and active lever responses in session 4. Data are the means ± SEM; n = 6–7/group.

Figure 8.

Number of infusions during the 4 hr session in 30 min blocks for male Wistar rats self-infusing 200 mg% EtOH into the posterior VTA during the first four sessions (only sessions 1 and 4 are shown), 200 mg% EtOH plus 100 μm quinpirole (Quin) in sessions 5 and 6 (only session 6 is shown), and 200 mg% EtOH μm quinpirole and 100 μm sulipride (Sulp) in sessions 7 and 8 (only session 8 is shown). Data are the means ± SEM; n = 6.