The molecular and cellular mechanisms that lead to compulsive drug use are believed to be similar to those involved normally in reward-related learning1. We found that although some of the neural substrates underlying both are conserved in flies, such as the mushroom body αβ neurons, there are distinct mechanisms that underlie the motivational properties of ethanol and sucrose as rewards. For example, whereas blocking output of dopaminergic neurotransmission does not directly affect 3 min memory for sucrose34, it disrupts 24 hr memory for ethanol reward. Intriguingly however, blocking output of the PPL1 cluster of TH+ neurons enhances 3 hr memory for sucrose reward in satiated flies22. This suggests that the neural substrates for memory of ethanol reward may overlap with the neural substrates that modify, but are not required for, memory of sucrose reward.
