Two related forms of memory in the crab Chasmagnathus are differentially affected by NMDA receptor antagonists Julieta Troncoso, He ´ctor Maldonado * Laboratorio de Neurobiologı ´a de la Memoria, Facultad de Ciencias Exactas y Naturales, Departamento Biologia, Universidad de Buenos Aires, Buenos Aires, Argentina Received 3 May 2001; received in revised form 1 October 2001; accepted 16 November 2001 Abstract A visual danger stimulus (VDS) elicits an escape response in the crab Chasmagnathus that declines after a few iterative presentations. Long-lasting retention of such decrement, termed context-signal memory (CSM), is mediated by an association between danger stimulus and environmental cues, cycloheximide sensitive, correlated with PKA activity and NFk-B activation, positively modulated by angiotensins, and selectively regulated by a muscarinic – cholinergic mechanism. The present research was aimed at studying the possible involvement of NMDA-like receptors in CSM, given the role attributed to these receptors in vertebrate memory and their occurrence in invertebrates including crustaceans. Vertebrate antagonists ( ± )-2-amino-5-phosphonopentanoic acid (AP5) and (+)-5-methyl-10,11-dihydro-5H-diben- zo[a,d]cyclohepten-5,10-imine (MK-801) were used. Memory retention impairment was shown with MK-801 10  3 M (1 mg/g) injected immediately before training or after training, or delayed 1 or 4 h, but not 6 h, posttraining. An AP5 10  3 M dose (0.6 mg/g) impairs retention when given before but not after training. Neither antagonist produced retrieval deficit. A memory process similar to CSM but nonassociative in nature and induced by massed training (termed signal memory, SM), proved entirely insensitive to AP5 or MK-801, confirming the view that distinct mechanisms subserve these different types of memory in the crab. D 2002 Elsevier Science Inc. All rights reserved. Keywords: Learning; Memory; NMDA; AP5: MK-801; Crab; Crustacea 1. Introduction An extensive series of experiments support the fact that NMDA receptors are implicated as mediators in several memory processes, e.g., spatial learning in the water or radial maze (Morris et al., 1986; Caramanos and Shapiro, 1994), inhibitory avoidance memory, (Jerusalinsky et al., 1992; Rickard et al., 1994; Burchuladze and Rose, 1992), early olfactory learning (Lincoln et al., 1988; Weldon et al., 1997), fear conditioning, (Miserendino et al., 1990), delayed conditional discrimination (Tan et al., 1989), brightness discrimination (Tang and Ho, 1988) and conditioned taste aversion (Gutie ´rrez et al., 1999). Such enhanced research on the role of NMDA receptors in neural learning mechanisms has resulted more from the discovery that these receptors are involved in induction of hippocampus LTP than for any other reason (Cain, 1997). Although grounded on very disparate learning paradigms, this research has been confined to vertebrate species alone. However, the occurrence of NMDA type of receptors in invertebrates has been often reported since their early description in the visual interneurons of crayfish by Pfeiffer-Lynn and Glantz (1991). In decapod crustaceans, several reports identify the presence of NMDA- related receptors by biochemical, immunostaining, Western blot analysis and electrophysiological techniques (Parnas et al., 1994, 1996; Feinstein et al., 1998; Schramm and Dudel, 1997; Burgess and Derby, 1997). Besides, the occur- rence of such type of glutamate receptors has also been documented in mollusks, namely, in isolated ganglia of gasteropods by electrophysiological techniques (Moroz et al., 1993; Kavaliers et al., 1997) and in tissues of bivalves by high-performance liquid chromatography (Todoroki et al., 1999). On the other hand, cDNA isolated from Drosophila has been described, which encodes a putative NMDA receptor protein that displays 46% amino acid identity to the rat NMDAR1 polypeptide (Ultsch et al., 1993). Never- theless, the role of NMDA in learning and memory processes 0091-3057/02/$ – see front matter D 2002 Elsevier Science Inc. All rights reserved. PII:S0091-3057(01)00779-1 * Corresponding author. Biologia, Ciudad Universitaria, Pabello ´n 2, 1428 Buenos Aires, Argentina. Tel.: +54-11-4576-3348; fax: +54-11-4576- 3384. E-mail address: hector@bg.fcen.uba.ar (H. Maldonado). www.elsevier.com/locate/pharmbiochembeh Pharmacology, Biochemistry and Behavior 72 (2002) 251–265