Role of D1-like and D2-like dopamine receptors within the ventral tegmental area in stress-induced and drug priming-induced reinstatement of morphine seeking in rats.

Abstract

The ventral tegmental area (VTA) as a major source of dopamine neurons projecting to cortical and limbic regions has a crucial role in reward as well as stress processes. Dopamine is a predominant neurotransmitter in the reward system, which plays an important role in both drug priming-induced and cue-induced reinstatement of cocaine and heroin seeking. It has been shown that this neurotransmitter has a role in stress-induced relapse to drug seeking. Therefore, the present study aims to evaluate the effects of intra-VTA administration of SCH-23390, as a dopamine D1-like receptor antagonist, and sulpiride, as a dopamine D2-like receptor antagonist, on drug priming-induced and food deprivation (FD)-induced reinstatement. The rats were bilaterally implanted by two separate cannulae into the VTA. After the acquisition and extinction of morphine-conditioned place preference, the animals received different doses of SCH-23390 or sulpiride (0.15, 0.4, 1.5 and 4 mg/0.3 µl vehicle per side) into the VTA on the reinstatement day and tested for drug priming-induced reinstatement of morphine (1 mg/kg) or FD-induced reinstatement facilitated by an ineffective dose of morphine (0.5 mg/kg) in separate groups. Our findings indicated that the D1/D2-like receptor antagonists attenuated the drug priming-induced and FD-induced reinstatement. However, these decrements were more significant in groups of animals that received a 24-h FD as a stressor. The data may suggest a role for the VTA dopaminergic system in relapse to drugs of abuse, which may be induced either by re-exposure to morphine or exposure to a stressor.