Behavioral devaluation by local resistance to dopamine.

Repeated experiences can cause behavior-specific fatigue. We use Drosophila to study this common form of motivational change, finding that prior matings make males more likely to abandon future copulations when challenged. Here we show that, during mating, dopamine signals through the D2-like receptor (D2R) to promote resilience to challenges that might otherwise cause the male to switch behaviors. This motivating dopamine signal suppresses the output of the copulation decision neurons (CDNs), which can truncate matings when pushed past threshold. Repetition-induced devaluation of mating results from β-arrestin-dependent desensitization of the D2R on the CDNs, rendering them temporarily resistant to naturally released or experimentally supplied dopamine. When local desensitization to dopamine is prevented, the male shows no signs of fatigue, treating each mating as if it were his first. These findings explain a widespread motivational phenomenon and reveal a natural function for the notorious susceptibility of the D2R to drug-induced desensitization.