N-methyl-d-aspartic acid receptors are altered by stress and alcohol in Wistar-Kyoto rat brain

Abstract

Previous studies have shown that the Wistar-Kyoto (WKY) rat strain is more sensitive to stressors and consumes significant quantities of alcohol under basal as well as stressful conditions when compared to other strains. Given that the glutamate neurotransmitter system has been implicated in depression and addiction, the goals of the present study were to investigate the effects of stress and stress-alcohol interactions on N-methyl-d-aspartate (NMDA) receptors in the rat brain. Thus this study measured the binding of [(3)H] MK-801 to NMDA receptors in the prefrontal cortex (PFC), caudate putamen (CPu), nucleus accumbens (NAc), hippocampus (HIP) and basolateral amygdala (BLA) in WKY rats in comparison to the Wistar (WIS) rat strain. Our results suggested that while voluntary alcohol consumption did not alter NMDA receptors in the PFC, CPu or NAc in either rat strain, it increased NMDA receptors in the HIP and BLA in both strains. In contrast, chronic stress increased NMDA receptors in the PFC, CPu, NAc in WKY rats but not in WIS rats. Chronic stress also decreased NMDA receptors in the HIP and increased NMDA receptors in the BLA in both strains. Alcohol co-treatment with stress increased NMDA receptors in the PFC, CPu and NAc in WKY rats but not in WIS rats. Interestingly, while alcohol co-treatment did not reverse stress induced decreases in NMDA receptors in the HIP, it reduced the binding of NMDA receptors in the BLA to control levels in both strains. Thus it appears that NMDA receptors in the PFC, CPu and NAc may be more sensitive to the effects of stress and could be implicated in the stress-induced alcohol consumption behavior seen in WKY rats. In contrast, NMDA receptors in the HIP and BLA may reflect an adaptive response and may not be responsible for the stress susceptible phenotype of the WKY rat strain.

Fig.1. Mean body weights of WIS and WKY rats over 24 days of experiment

Data are expressed as the mean body weights of 6-8 rats from each group over 24 days of experiment. No significant change in weights was noted following treatment with AL, CS and CS-AL, compared to their respective control group, Student's t test, P>0.05. Control: control group; AL: alcohol group; CS: chronic stress group; CS-AL: co-treatment with alcohol and chronic stress group.

Fig.2. Effects of alcohol, chronic stress and co-treatment with alcohol and chronic stress on the binding of [³H] MK-801 to NMDA receptor in the prefrontal cortex in WKY and WIS rats

Data are expressed as the mean ± S.E.M. of measurements from 6-8 rats from each strain, with determinations made in duplicate sections from each brain. * Represents significant differences between treatment groups within strain, Tukey HSD test, P<0.05; † and ‡ represent significant differences between WKY and WIS within Control groups and AL groups respectively, Tukey HSD test, P<0.05. Control: control group; AL: alcohol group; CS: chronic stress group; CS-AL: co-treatment with alcohol and chronic stress group.

Fig.3. Effects of alcohol, chronic stress and co-treatment with alcohol and chronic stress on the binding of [³H] MK-801 to NMDA receptor in the caudate putamen in WKY and WIS rats

Data are expressed as the mean ± S.E.M. of measurements from 6-8 rats from each strain, with determinations made in duplicate sections from each brain. * Represents significant differences between treatment groups within strain, Tukey HSD test, P<0.05. †, ‡, @ and ♯ represent significant differences between WKY and WIS within their respective treatment groups, Tukey HSD test, P<0.05. Control: control group; AL: alcohol group; CS: chronic stress group; CS-AL: co-treatment with alcohol and chronic stress group.

Fig.4. Effects of alcohol, chronic stress and co-treatment with alcohol and chronic stress on the binding of [³H] MK-801 to NMDA receptor in the nucleus accumbens in WKY and WIS rats

Data are expressed as the mean ± S.E.M. of measurements from 6-8 rats from each strain, with determinations made in duplicate sections from each brain. * Represents significant differences between treatment groups within strain, Tukey HSD test, P<0.05. †, ‡ and ♯ represent significant differences between WKY and WIS within their respective treatment groups, Tukey HSD test, P<0.05. Control: control group; AL: alcohol group; CS: chronic stress group; CS-AL: co-treatment with alcohol and chronic stress group.

Fig.5. Effects of alcohol, chronic stress and co-treatment with alcohol and chronic stress on the binding of [³H] MK-801 to NMDA receptor in the hippocampus in WKY and WIS rats

Data are expressed as the mean ± S.E.M. of measurements from 6-8 rats from each strain, with determinations made in duplicate sections from each brain. * Represents significant differences between treatment groups within strain, Tukey HSD test, P<0.05. †, ‡ and @ represent significant differences between WKY and WIS within their respective treatment groups, Tukey HSD test, P<0.05. Control: control group; AL: alcohol group; CS: chronic stress group; CS-AL: co-treatment with alcohol and chronic stress group.

Fig.6. Effects of alcohol, chronic stress and co-treatment with alcohol and chronic stress on the binding of [³H] MK-801 to NMDA receptor in the basolateral amygdala in WKY and WIS rats

Data are expressed as the mean ± S.E.M. of measurements from 6-8 rats from each strain, with determinations made in duplicate sections from each brain. * Represents significant differences between treatment groups within strain, Tukey HSD test, P<0.05. Control: control group; AL: alcohol group; CS: chronic stress group; CS-AL: co-treatment with alcohol and chronic stress group.