Ketamine blocks a taste recognition memory in fetal rats

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Abstract

Decisions about novelty/familiarity are critical in determining whether or not information should be attended to, and possibly encoded, for long-term storage. We have reported that fetal and neonatal rats exhibit an increase in orofacial movements (e.g., perseverative mouthing and mouth movements, and licks) upon tasting saccharin (SAC), if it was experienced previously. E19 rat fetuses can acquire this taste recognition memory and retain it for at least 5 days (P3). In the current study, we sought to evaluate the role of N-methyl-d-aspartate (NMDA) receptors in establishing a taste recognition memory. Pregnant Sprague–Dawley rats received ketamine (NMDA receptor antagonist) (doses: 0, 50, or 100 mg/kg, ip). One-half hour later, we performed a reversible spinal block on each pregnant dam, and E19 fetuses received an oral injection of 10 μl, 0.3% SAC or water (control) while in utero. The uterus was replaced and the pups were later born via a normal vaginal delivery. On P3, all pups experienced oral lavage of 10 μl, 0.3% SAC, and motor responses were recorded. As expected, non-drugged control neonates tasting familiar SAC exhibited significantly more perseverative mouth movements, as well as total mouth movements and licks, than did pups tasting novel SAC. However, this taste recognition memory response was not observed in rats exposed to ketamine in utero. The data suggest that early non-associative taste memories may be disrupted by NMDA receptor blockade.

Section snippets

Subject

The subjects were perinatal Sprague–Dawley rats (male and female) obtained from timed-pregnant female rats supplied by Zivic-Miller Laboratories (Zelienople, PA). The date of conception (i.e., the first day that a vaginal plug was detected) was designated as “embryonic day 0” (E0). Pregnant animals (from which our subjects were derived) were individually housed in plastic “shoe box” cages (44.45 cm long×21.59 cm wide×20.32 cm high). Home cage temperature was maintained at 23–26°C under a

Results

The current data indicate that perinatal rats can discriminate between a novel and familiar taste. On P3, control rats (i.e., those that did not receive ketamine on E19) previously treated with SAC, exhibited significantly more mouth movements and licks than rats previously treated with water on E19 (see Fig. 1). Similarly, perseverative mouth movements were much more prominent in neonates tasting familiar SAC (see Fig. 2). The ANOVA of the mouthing and licking data revealed a significant SAC

Discussion

The data presented here indicate that P3 neonatal rats exhibited different orofacial movements depending on whether the taste of SAC was novel or familiar. The frequency of mouthing and licking responses is enhanced following lavage with familiar SAC and relatively suppressed after novel SAC. Ketamine administered before the initial taste manipulation (on E19) significantly reduced the differential response to novel vs. familiar SAC 5 days later.

The behaviors associated with this taste

Acknowledgements

The authors wish to thank David Revta and William Liggett for their assistance in building the neonatal testing unit. The following students and colleagues at Baldwin-Wallace College provided excellent technical support in these studies: Amy Booth, Kathryn Bryan, April Carter, Christine Dengler, Dominic Donnellan, Ben Girdler, Cynthia Kenmuir, Nadia Lelutiu, Colleen McMullen, Lora Pagel, Anaibelith Perez, Kristie Randall, Louie Rundo, Erin Simon, Tennille Lewis, Melissa Vanderkaay, Jessica

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