d-Cycloserine enhances conditioned taste aversion learning in rats

Abstract

Conditioned taste aversion (CTA) is a form of associative learning in which the pairing of a taste with a toxin causes an animal to avoid the taste. NMDA receptor mediated neurotransmission has been implicated in CTA, but the role of the NMDA receptor glycine-binding site has not been examined. To examine the effects on CTA of the glycinergic NMDA receptor agonist D-cycloserine, rats received D-cycloserine (15 mg/kg, i.p.) or vehicle 15 min before 10-min access to 0.125% saccharin, followed by a low dose of LiCl (19 mg/kg, i.p.). CTA was measured with 24-h, 2-bottle preference tests between water and saccharin. Vehicle-treated rats formed a mild CTA that rapidly extinguished, while D-cycloserine-treated rats formed a stronger CTA that extinguished slowly. The effect of D-cycloserine was specific to the NMDA receptor glycine-binding site, because pretreatment with HA-966 (6 mg/kg), a partial glycinergic agonist, blocked enhancement by Dcycloserine. Three follow-up experiments suggest that the enhancement of CTA was not due to an aversive effect of D-cycloserine. First, saccharin paired with D-cycloserine (15 mg/kg) alone did not induce a CTA, although a higher dose (30 mg/kg) did significantly lower saccharin preference. Second, pretreatment with D-cycloserine did not increase the duration of "lying-on-belly" behavior induced by LiCl. Third, pretreatment with D-cycloserine did not increase c-Fos induction by either LiCl or vehicle injection in central visceral relays (the nucleus of the solitary tract, the parabrachial nucleus, the central nucleus of the amygdala, the supraoptic nucleus, and the paraventricular nucleus). These results confirm the participation of NMDA receptor, and specifically the glycine-binding site of NMDA receptor, in CTA learning.

d-cycloserine enhances short-delay, but not long-delay, conditioned taste aversion learning in rats

“…Consistent with a prior study (Land & Riccio, 1997), our laboratory has shown that systemic DCS (7 or 15mg/kg) dose-dependently enhanced CTA learning in rats when administered before a saccharin-LiCl pairing (Nunnink et al, 2007). This enhancement by DCS was not due to increased malaise or increased neural responsiveness to the toxin, because DCS administered without LiCl did not produce a CTA, DCS did not increase LiCl-induced “lying-on-belly” behavior, and DCS did not increase LiCl-induced c-Fos in central visceral relays such as the nucleus of the solitary tract, parabrachial nucleus, central nucleus of the amygdala, supraoptic nucleus, and paraventricular nucleus.…”

“…or isotonic saline (1 ml/kg) as a control vehicle. This dose of DCS was chosen based on our previous report because it produced a maximal enhancement of CTA but had no aversive effects on its own (Nunnink et al, 2007). DCS was administered 15 or 60 min prior to conditioning, because a pharmacokinetic study has shown that DCS reaches the brain 15 and 60 min after systemic administration in rats (Baran et al, 1995).…”

D-cycloserine in Prelimbic Cortex Reverses Scopolamine-Induced Deficits in Olfactory Memory in Rats

“…In this regard, there is evidence showing, on the one hand, that DCS facilitated ODT [15], conditioned fear responses [64], [65], [66], conditioned flavor-taste preference and conditioned-taste aversion [13], [67], or procedural learning in humans [68]. On the other hand, no facilitative effects of DCS administration were found in the retention of Morris water maze (MWM) learning in rodents [69], [70], or declarative word-pair learning in humans [68].…”

d-Cycloserine for the augmentation of an attentional training intervention for trait anxiety

“…DCS has performed poorly in applications of this singledose paradigm to non-emotional memory tasks that do not involve extinction in humans (Otto et al, 2009;Goff et al, 2008). However, animal models have suggested that DCS facilitates other types of memory in tasks that may involve limbic activation, such as spatial memory (Land & Riccio, 1999;Lelong, Dauphin, & Boulouard, 2001) and taste aversion acquisition (Davenport & Houpt, 2009;Nunnink, Davenport, Ortega, & Houpt, 2007). Similarly, in humans, a recent study showed that DCS can facilitate the retention of fear conditioning using mild electric shock as a stimulus (Kalisch et al, 2009).…”