Involvement of dopamine D-2 autoreceptors in the ventral tegmental area onalcohol and saccharin intake of the alcohol-preferring P rat

Background: The ventral tegmental area (VTA) dopamine (DA) system is consid ered to be involved in mediating the actions of ethanol (EtOH). The objecti ve of the present study was to examine the role of VTA DA D-2 receptors in regulating EtOH intake of alcohol-preferring P rats. Methods: EtOH (10% v/v) and saccharin (SACC, 0.012546 g/v) intake during 2 hr of limited access was assessed after microinjections of the D-2, agonist quinpirole and the D-2, antagonist sulpiride into the anterior VTA (AVTA) of female P rats. Both EtOH-SACC alternate-day-access conditions and daily availability of EtOR and SACC solutions to separate groups of subjects were used. A second D-2 agonist, quinelorane. and coadministration of 2.0 mu g sulpiride with 2.0 mu g quinpirole were tested in animals given limited acc ess to EtOH. Finally, the effects of quinpirole injected 2 mm dorsal to the VTA and within the posterior VTA (PVTA) were assessed under EtOH-SACC alte rnate-day-access conditions. Results: Microinjections of 2.0-6.0 mu g quinpirole into the AVTA dose depe ndently decreased EtOH intake 40-80% during the first 30 min of the limited access sessions but did not alter SACC intake. Injections of 2.0-4.0 mu g quineloranc into the AVTA also reduced EtOH intake in the first 30 min. Adm inistration of 0.5-2.0 mu g sulpiride into the AVTA had no effect on either EtOH or SACC intakes but did attenuate the effects of quinpirole on reduci ng EtOH intake. Injections of 2.0-4.0 quinpirole 2 mm dorsal To the VTA did not alter EtOH or SACC intakes. Posterior VTA injections of quinpirole dec reased EtOH and SACC intakes approximately 25-30% and 60-70%, respectively, in the first 30 min. None of the treatments altered intakes during the 30- 120 min period. Conclusions: The data suggest that DA neuronal activity within the AVTA may be important for maintaining EtOH drinking in P rats, whereas DA neuronal activity within the PVTA may be involved in regulating general drinking and /or motivational behaviors. Overall, the results confirm the involvement of mesolimbic DA in EtOH self-administration and suggest that there is functi onal heterogeneity within the VTA regulating drinking behavior of the P rat .