Strain differences in the distribution of N-methyl-d-aspartate and gamma (gamma)-aminobutyric acid-A receptors in rat brain

Abstract

Aims: Previous studies have shown that the Wistar-Kyoto (WKY) rat strain exhibits depressive symptoms such as anhedonia, psychomotor retardation, ambivalence and negative memory bias following exposure to stress. Given the involvement of excitatory glutamate and inhibitory gamma (gamma)-aminobutyric acid (GABA) signaling pathways in influencing depressive behavior, the present study investigated strain differences in the distribution of central N-methyl-d-aspartate (NMDA) and GABA(A) receptor sites in WKY compared to their inbred counterpart, Wistar (WIS) rats.

Main methods: Quantitative autoradiographic analysis was used to map the binding and distribution of NMDA and GABA(A) receptors in various brain regions in WKY and WIS rats.

Key findings: Results indicated a significant difference between the two strains. Lower NMDA receptor binding was found in the anterior cingulate cortex, caudate putmen, nucleus accumbens, CA1 region of the hippocampus and the substantia nigra pars reticulata in WKY compared to WIS rats. Conversely, higher GABA(A) receptor binding was found in the amygdala, caudate putmen, dentate gyrus, CA2 and CA3 fields of the hippocampus, periaqueductal grey and substantia nigra pars reticulata in WKY compared to WIS rats.

Significance: Given that these two rat strains differ in their behavioural, endocrine and neurochemical profile, the observed strain differences in NMDA and GABA(A) receptor binding suggest that these two neurotransmitter systems may be involved in the depressive and stress-sensitive phenotype of the WKY rat strain.

Fig. 1

Representative autoradiographs from Plates 12, 30 and 42 showing total [³H] MK-801 binding to NMDA receptors (A) and [³H] SR95531 binding to GABA_A receptors (B) in WKY rat (right) and comparison WIS rat (left) brains.