Involvement of hippocampal NMDA receptors in retention of shuttle avoidance conditioning in rats

Abstract

The purpose of this research was to evaluate the role of hippocampal N-methyl-D-aspartate (NMDA) receptors in acquisition and consolidation of memory during shuttle avoidance conditioning in rats. Adult male Wistar rats were surgically implanted with cannulae aimed at the CA1 area of the dorsal hippocampus. After recovery from surgery, animals were trained and tested in a shuttle avoidance apparatus (30 trials, 0.5-mA footshock, 24-h training-test interval). Immediately before or immediately after training, animals received a bilateral intrahippocampal 0.5-µl infusion containing 5.0 µg of the NMDA competitive receptor antagonist aminophosphonopentanoic acid (AP5) or vehicle (phosphate-buffered saline, pH 7.4). Infusion duration was 2 min per side. Pre-training infusion of AP5 impaired retention test performance (mean ± SEM number of conditioned responses (CRs) during retention test session was 16.47 ± 1.78 in the vehicle group and 9.93 ± 1.59 in the AP5 group; P<0.05). Post-training infusion of AP5 did not affect retention (mean ± SEM number of conditioned responses during retention test session was 18.46 ± 1.94 in the vehicle group and 20.42 ± 2.38 in the AP5 group; P>0.10). This impairment could not be attributed to an effect on acquisition, motor activity or footshock sensitivity since AP5 affected neither training session performance measured by the number of CRs nor the number of intertrial crossings during the training session. These data suggest that NMDA receptors in the hippocampus are critical for retention of shuttle avoidance conditioning, in agreement with previous evidence showing a role of NMDA receptors in fear memory. Key wordsThe N-methyl-D-aspartate (NMDA) glutamate receptor channel has been implicated in learning and memory for several tasks. Intraventricular infusion of the NMDA receptor competitive antagonist aminophosphonopentanoic acid (AP5) impairs acquisition in the Morris water maze (1). Both intraventricular (2) and intrahippocampal (3) infusions of AP5 given before training block memory of fear conditioning measured 24 h later. Also, immediate post-training intrahippocampal infusion of AP5 impairs retention of a step-down inhibitory avoidance task (4-7). Taken together, these data provide evidence for the involvement of the dorsal hippocampus in fear memory through an NMDA receptor-dependent mechanism. It has been suggested that the impairing effects of intra-

NMDA Receptors Mediate Consolidation of Contextual Memory in the Hippocampus after Context Preexposure

“…Animals were implanted under thionembutal anesthesia (30 mg/kg, ip) with bilateral 9.0 mm guide cannulae aimed 1.0 mm above the CA1 area of the dorsal hippocampus as previously described (6)(7)(8). Coordinates (anteroposterior, )4.3 mm from bregma, mediolateral, ±3.0 mm from bregma, ventral, )1.4 mm from dura) were obtained from the atlas of Paxinos and Watson (16).…”

“…Immediately after inhibitory avoidance training or context preexposure, an infusion needle was fitted into the guide cannula. The tip of the infusion needle protruded 1.0 mm beyond the guide cannula and was aimed at the CA1 area of the dorsal hippocampus as previously described (6)(7)(8). A bilateral 0.5-ll infusion volume of vehicle (VEH; phosphate buffer in saline, pH 7.4) or AP5 (5.0 lg; Sigma-RBI, Natick, MA) dissolved in the vehicle was given during a 1-min infusion period.…”

“…Twenty-four to 48 h after behavioral testing, the animals were killed by decapitation and their brains were removed, stored in 5% formalin for at least 72 h and verified for infusion site placements in the dorsal hippocampus as described in previous reports (6)(7)(8). Only data from animals with correct (i.e., within 1 mm 3 of the intended site) placements of infusion needles in the CA1 area of the dorsal hippocampus (89% of the animals) were included in the final analysis (Fig.…”

“…Extensive evidence from genetic (1-3) and pharmacological (4)(5)(6)(7)(8)(9) studies have implicated the N-methyl-D-aspartate (NMDA) type of glutamate receptor channel in the formation of memory for different types of aversive conditioning in the dorsal hippocampus (for recent reviews, see (10,11)). When infused into the CA1 area of the rat dorsal hippocampus after training, the NMDA receptor antagonist aminophosphonopentanoic acid (AP5) blocks consolidation of step-down inhibitory avoidance (IA), a single-trial type of aversively motivated conditioning (4,7,8).…”

Out of Context: NMDA Receptor Antagonism in the Avian 'Prefrontal Cortex' Impairs Context Processing in a Conditional Discrimination Task.

“…Although there are a few exceptions (Lee, Choi, Brown, & Kim, 2001;Roesler, Kuyven, Kruel, Quevedo, & Ferreira, 1998), unimpaired recall has been demonstrated for various conditioning scenarios (Baron & Moerschbaecher, 1996;Bohn et al, 2003;Churchill et al, 2001;Di Ciano, Cardinal, Cowell, Little, & Everitt, 2001;Kelley et al, 1997;Smith-Roe et al, 1999;Xu, Bazner, Qi, Johnson, & Freidhoff, 2003). However, in most of these studies, the requirement was to recall unambiguous stimulus-response associations, with one stimulus being the Sϩ and the other being the SϪ.…”