The terrestrial slug Limax is able to acquire short-term and long-term memories during aversive odor-taste associative learning. We investigated the effect of the selective serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) on memory. Behavioral studies indicated that 5,7-DHT impaired short-term memory but not long-term memory. HPLC (high-performance liquid chromatography) analysis revealed that 5,7-DHT significantly reduced serotonin content in the central nervous system. The present study suggests that acquisition, retention, and/or retrieval of short-term memory involves serotonin, and neither acquisition nor retrieval of long-term memory requires serotonin at a level as high as that required for short-term memory.The land slug Limax has a highly developed olfactory system and exhibits aversive odor-taste associative learning (Sahley et al. 1981). It avoids the odor of innately attractive food (e.g., carrot or cucumber), the conditioned stimulus (CS), following conditioning by a paired presentation of the CS and the bitter-taste of quinidine, which is a noxious unconditioned stimulus (US). This behavioral change persists for at least two weeks even after only one conditioning trial (Matsuo et al. 2002). Extensive behavioral analyses have been done, and the properties of the memory have been characterized (Sahley et al. 1981;Yamada et al. 1992). The central networks involved in odor processing and memory have also been extensively studied by physiological methods and are well documented (Gelperin and Tank 1990; Kimura et al. 1998a,b,c;Watanabe et al. 1998Watanabe et al. , 1999Watanabe et al. , 2003Inoue et al. 2004). However, the molecular mechanisms for this learning are only partly understood. Elucidation of the neurotransmitters and neuromodulators, especially those involved in learning, will be a key step toward understanding the mechanisms of odor learning.Based on previous findings, serotonin is likely to play an important role in learning. First, the procerebral (PC) lobe of Limax, which is the putative site where learning is thought to occur (Kimura et al. 1998a), receives serotonergic projections (Osborne and Cottrell 1971;Inoue et al. 2004). Many serotonincontaining neurons are found in the central nervous system (CNS) of Limax (Shirahata et al. 2004). Second, biochemical and electrophysiological changes in the PC lobe are triggered by serotonin Gelperin 1987, 1989;Gelperin et al. 1993). Also, in Aplysia (another mollusk), serotonin is essential for gill withdrawal learning (Glanzman et al. 1989), although this is a simple reflex type of learning. However, there have been no behavioral data that directly indicate whether serotonin is involved in the odor learning of Limax. In the present study, we asked if serotonin is actually involved in aversive odor-taste associative learning.Memories are divided into short-term and long-term phases. Memory in Limax is not affected by protein synthesis inhibitors up to one day after conditioning, while memories that persist two or more days after conditi...