Metabotropic glutamate receptor antagonists but not NMDA antagonists affect conditioned taste aversion acquisition in the parabrachial nucleus of rats.

The effect of glutamate receptor antagonists on conditioned taste aversion (CTA) was studied in rats. The association of the short-term memory of a gustatory conditioned stimulus (CS) with visceral malaise (unconditioned stimulus, US) in the CTA paradigm takes place in the parabrachial nuclei (PBN) of the brainstem. The first direct evidence of participation of glutamatergic neurotransmission in the PBN during CTA demonstrated that the extracellular level of glutamate rises during saccharin drinking (Bielavska et al. in Brain Res 887:413-417, 2000). Our results show an effect of microdialysis administration of selective GluR antagonists into the PBN on the formation of CTA engram. We used four glutamate receptor (GluR) antagonists of different types (D-AP5, MK-801 as antagonists of ionotropic GluR and L-AP3, MSPG as antagonists of metabotropic GluR). The disruptive effect of MK-801 on CTA formation in the PBN is concentration-dependent, with the greatest inhibition under the higher concentrations eliciting significant disruption. The application of D-AP5 (0.1, 1, 5 mM) did not elicit a statistically significant blockade of CTA acquisition. This indicates that the association of the US-CS in the PBN is not dependent on NMDA receptors. On the contrary, application of L-AP3 (0.1, 1, 5 mM) blocked the CS-US association.

Genome scanning of the HXB/BXH sets of recombinant inbred strains of the rat for quantitative trait loci associated with conditioned taste aversion.

In the current study, we searched for quantitative trait loci (QTL) responsible for a conditioned taste aversion (CTA) measured as a decrease in the intake of a saccharin conditioned stimulus followed by an i.p. injection of 0.15 M LiCl (lithium chloride) (2 ml/100 g body weight). A genome scanning for QTL associated with CTA was performed in the HXB/BXH sets of recombinant inbred (RI) strains derived from the Brown Norway (BN-Lx) rat and the spontaneously hypertensive rat (SHR). The BN-Lx progenitor showed a significantly stronger CTA (8.3+/-2.8%) than the SHR progenitor (27.8+/-3.3%, p < .0001). The distribution of CTA values among RI strains was continuous, suggesting a polygenic mode of inheritance. Genome scanning of RI strains with more than 700 gene markers revealed a significant association of CTA with the D2Cebr11s4 marker on chromosome 2 (LRS = 22.7) and with the D4Cebrp149s8 marker on chromosome 4 (LRS = 23.4). The chromosome 2 putative QTL was confirmed by detecting a significant difference in CTA between the SHR progenitor (27.8+/-3.3%) and the SHR-2 (SHR.BN-D2Rat171/D2Arb24) congenic strain (13.1+/-4.4%, p < .01) that are genetically identical except for a segment of chromosome 2 that was transferred onto the genetic background of the SHR from the BN strain.