Environmental stimuli associated with a single cocaine exposure acquire long-lasting motivational properties that are able to induce relapse. We measured Brain-derived neurotrophic factor (BDNF) and dopamine D3 receptor (Drd3) expressions in rat brain regions that have been involved in drug-conditioning. Acute cocaine produced a transient increase in BDNF mRNA in the prefrontal cortex, associated with a long-lasting increase in drd3 mRNA, and a delayed and long-lasting increase in Drd3 protein in the nucleus accumbens. Methamphetamine and morphine, two drugs known to easily induce drug-conditioning, also markedly elevated BDNF mRNA. Nicotine had more limited effects. Abused drugs increase acutely BDNF expression, which leads to subsequent long-lasting elevation of Drd3 in the nucleus accumbens that may facilitate responding to drug-associated stimuli.