Research reportMicroinjections of a dopamine D1 receptor antagonist into the ventral tegmental area block the expression of cocaine conditioned place preference in rats

- The selective D1 antagonist, SCH 23390, injected into the VTA blocks cocaine conditioned place preference.
- Dendritically released dopamine in the VTA plays a role in cocaine conditioned place preference.
- Cocaine-seeking related behaviors depend on VTA dopamine D1 receptor stimulation.

Stimulation of dopamine (DA) D1 receptors in the ventral tegmental area (VTA) is involved in primary rewards. In the current study we investigated whether VTA D1 receptor stimulation likewise plays a role in mediating the rewarding effects of cocaine-associated stimuli, using the cocaine conditioned place preference (CPP) paradigm. Rats were prepared with cannulae so as to allow microinjections in the VTA and later conditioned to a cocaine-associated environment using the CPP paradigm. Prior to each conditioning session rats were injected with either saline or cocaine (10 mg/kg, intraperitoneally) and then placed in one of the two sides of the CPP apparatus. Sessions lasted 30 min a day over a period of eight days, such that rats alternated daily between consistently experiencing cocaine in one side and saline in the other. On the test day, which was conducted one day after conditioning, rats were given bilateral microinjections of one of four doses of the D1 antagonist, SCH 23390, (0, 2, 4 or 8 μg/0.5 μl) directly into the VTA and allowed free access to both sides of the apparatus. Preference for either side was measured as time spent in each side and compared to the same measures taken before conditioning. The D1 antagonist produced a dose-related, significant reduction in the preference for the cocaine-paired side compared to vehicle. These data suggest that the expression of cocaine conditioned place preference requires stimulation of VTA D1 receptors and, as such, are the first to suggest a role for VTA dendritically released DA in cocaine-, or other reward-, related learning.