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.
Exposure of rats to high strength static magnetic fields of 7 T or above has behavioral effects such as the induction of locomotor circling, the suppression of rearing, and the acquisition of conditioned taste aversion (CTA). To determine if habituation occurs across magnetic field exposures, rats were pre-exposed two times to a 14 T static magnetic field for 30 min on two consecutive days; on the third day, rats were given access to a novel 0.125% saccharin prior to a third 30-min exposure to the 14 T magnetic field. Compared to sham-exposed rats, pre-exposed rats showed less locomotor circling and an attenuated CTA. Rearing was suppressed in all magnet-exposed groups regardless of pre-exposure, suggesting that the suppression of rearing is more sensitive than other behavioral responses to magnet exposure. Habituation was also observed when rats under went pre-exposures at 2-3 hour intervals on a single day. Components of the habituation were also long lasting; a diminished circling response was observed when rats were exposed to magnetic field 36 days after 2 pre-exposures. To control for possible effects of unconditioned stimulus pre-exposure, rats were also tested in a similar experimental design with two injections of LiCl prior to the pairing of saccharin with a third injection of LiCl. Pre-exposure to LiCl did not attenuate the LiCl-induced CTA, suggesting that 2 pre-exposures to an unconditioned stimulus are not sufficient to explain the habituation to magnet exposure. Because the effects of magnetic field exposure are dependent on an intact vestibular apparatus, and because the vestibular system can habituate to many forms of perturbation, habituation to magnetic field exposure is consistent with mediation of magnetic field effects by the vestibular system.
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