Research reportΔ9-THC and WIN55,212-2 affect brain tissue levels of excitatory amino acids in a phenotype-, compound-, dose-, and region-specific manner

Endocannabinoids are involved in excitatory neurotransmission initiated by glutamate and aspartate. The aim of the present study was to investigate the effects of the cannabinoid agonists, Δ9-THC and WIN55,212-2, on tissue (prefrontal cortex, dorsal striatum, nucleus accumbens, hippocampus, amygdala and hypothalamus) levels of glutamate and aspartate in two rat phenotypes, high responders (HR) and low responders (LR), differentiated according to their response to a novel environment. HR displayed increased motor activity but no difference in basal levels of glutamate and aspartate as compared to LR. Both cannabinoids increased ambulatory activity at the low doses, this effect was observed only in HR following Δ9-THC, but in both HR and LR following WIN55,212-2. The cannabinoids primarily increased glutamate levels in the prefrontal cortex, dorsal striatum, nucleus accumbens and hippocampus, while the high dose of WIN55,212-2 decreased glutamate levels in the amygdala and both doses in the hypothalamus; these effects appeared overall more pronounced in HR. In contrast, the cannabinoids primarily decreased aspartate levels in all brain regions, except in the dorsal striatum, where an increase was seen after both doses of Δ9-THC and WIN55,212-2 as well as in the nucleus accumbens after the low dose of Δ9-THC in HR; these effects also appeared overall more pronounced in HR. Present results show that exogenous cannabinoids affect tissue levels of glutamate and aspartate in a phenotype-, compound-, dose-, and brain region-dependent manner.

► A study of cannabinoids' effects on glutamate/aspartate in high/low responder rats. ► Δ9-THC and WIN55,212-2 modulated glutamate/aspartate in a differential manner. ► Both compounds affect brain glutamate/aspartate phenotype- and dose-dependently. ► These cannabinoid-induced effects were also region-specific.