A transient, protein synthesis-independent long-term potentiation (early-LTP, <4 h) can be reinforced into a maintained protein synthesis-dependent late-LTP (>4 h) by specific electrical stimulation of limbic structures (J. Neurosci. 21 (2001) 3697). Similarly, LTP-modulation can be obtained by behavioral stimuli with strong motivational content. However, the requirement of protein synthesis during behavioral reinforcement has not been shown so far. Thus, we have studied here this specific question using a behavioral reinforcement protocol, i.e. allowing water-deprived animals to drink 15 min after induction of early-LTP. This procedure transformed early-LTP into late-LTP. Anisomycin, a reversible protein synthesis inhibitor, abolished behavioral LTP-reinforcement. These results demonstrate that behavioral reinforcement depends on protein synthesis.