NMDA receptor in conditioned flavor-taste preference learning: Blockade by MK-801 and enhancement by D-cycloserine

Abstract

Conditioned flavor-taste preference (CFTP) is a robust form of learning in which animals acquire a preference for a flavor (e.g. Kool-Aid) previously mixed with a highly preferred tastant (e.g. fructose) over a flavor previously mixed with a less preferred tastant (e.g. saccharin). Here, the role of the Nmethyl-D-aspartate (NMDA) glutamate-glycine receptor (NR) was probed using systemic MK-801, a non-competitive antagonist, and D-cycloserine (DCS), a glycine agonist. Rats were injected with MK-801 (100 μg/kg) or vehicle 30 min prior to a daily 2-h conditioning session with 1-bottle access to a Kool-Aid flavor (grape or cherry) mixed with either 8% fructose (CS+/F) or 0.2% saccharin (CS −/S). CFTP expression was measured in 2-bottle preference tests between the Kool-Aid flavors mixed with 0.2% saccharin (CS+/S vs. CS−/S). While vehicle-treated rats acquired a preference for CS+/ S over CS−/S, MK-801 prior to conditioning completely blocked CFTP learning. The effect of MK-801 was specific to CFTP acquisition, because follow-up experiments demonstrated that MK-801 did not induce a conditioned taste aversion, cause state-dependent learning, or affect CFTP expression. In a second approach, rats were injected with DCS (15 mg/kg) 60 min prior to daily conditioning. In contrast to MK-801, adminstration of DCS prior to conditioning enhanced CFTP learning (but not reversal conditioning). These results demonstrate that NR neurotransmission is critical for CFTP learning. Furthermore, enhancement of CFTP learning by DCS suggests that endogenous levels of glycine or D-serine may be a limiting factor in CFTP learning.

NMDA receptor antagonism differentially reduces acquisition and expression of sucrose- and fructose-conditioned flavor preferences in BALB/c and SWR mice

“…These data are highly consistent with the abilities of systemic MK-801 to eliminate the acquisition of fructose-CFP in rats (Golden and Houpt, 2007), and of amygdala administration of the competitive NMDA antagonist, AP-5 to eliminate the acquisition of CFP elicited by IG glucose (Touzani et al, 2013). The present study also demonstrated a clear strain difference in the potency of MK-801 to block the acquisition of sugar preferences.…”

“…MK-801, eliminated fructose-CFP acquisition, but not expression (Golden and Houpt, 2007). Further, the competitive NMDA antagonist, AP-5 administered into the rat amygdala eliminated acquisition, but not expression of a CFP induced by IG glucose (Touzani et al, 2013).…”

“…at 10 ml/kg body weight. The 100 µg/kg dose was chosen based on the testing of fructose-CFP acquisition and expression in rats (Golden and Houpt, 2007), whereas a higher 200 µg/kg dose was chosen for its effectiveness in blocking foodanticipatory activity rhythms in rats (Ono et al, 1996). …”

Role of systemic endocannabinoid CB-1 receptor antagonism in the acquisition and expression of fructose-conditioned flavor–flavor preferences in rats

“…Another neurotransmitter system implicated in flavor conditioning is the glutamatergic system. The non-competitive NMDA receptor antagonist, MK-801 was observed to reduce the acquisition, but not expression of fructose-conditioned flavor preferences, whereas the glycine agonist, D-cycloserine enhanced this response (Golden and Houpt, 2007). It may be that dopamine interacts with different neurotransmitter systems in mediating different aspects (e.g., acquisition, expression) of flavor-flavor preference learning.…”

“…The NMDA glutamate-glycine receptor has been implicated in flavor-flavor preferences in that the acquisition, but not the expression, of fructose-conditioned flavor preferences was respectively reduced by systemic administration of the non-competitive NMDA antagonist, MK-801, and enhanced by systemic administration of the glycine agonist, D-cycloserine (Golden and Houpt, 2007). Although the general opioid antagonist, naltrexone, is capable of reducing intakes of sucrose and saccharin solutions (see review, Bodnar, 2004), systemic administration of naltrexone failed to alter the acquisition or expression of sucroseconditioned flavor-flavor preferences in sham-feeding rats (Yu et al, 1999), of fructoseconditioned flavor-flavor preferences in real-feeding rats (Baker et al, 2004), or of sucroseconditioned flavor-nutrient preferences following IG infusions (Azzara et al, 2000).…”