A proteomic analysis of the behavioural effects of sugar cross-sensitisation with methamphetamine in the nucleus accumbens

The ease in accessibility to sugar-rich products has contributed to a dramatic increase in the consumption of sugar among the adolescent population. Likewise, due to its reinforcing properties, methamphetamine (METH) abuse and its associated mental health problems are another global burden. Both sugar and METH elicit their effects on similar neuronal systems, primarily the mesolimbic dopaminergic system which regulates the nucleus accumbens (NAc) of the brain. This study aimed to investigate the effects of chronic sugar consumption during adolescence on METH-induced locomotor activity in adulthood and associated changes to protein levels in the NAc of rats. Following 4 weeks of chronic sugar or water exposure, and a 6 week treatment-free period, rats were challenged with METH or vehicle and their locomotor behaviour measured. Following 24 hours, changes in protein levels in the NAc were identified using a proteomic approach. In comparison to the controls treated with water and challenged with saline (Water/Saline), the Water/METH group demonstrated significantly greater locomotor activation (p < 0.05). Providing support for behavioural cross-sensitisation, the Sugar/METH condition significantly demonstrated greater locomotor activity compared to the Water/METH condition (p < 0.05). Proteomic analyses revealed that a total of 93 differentially expressed proteins were identified in the NAc of the Water/METH rats compared to controls. These proteins were mainly involved in coordinating mitochondrial functioning and neuronal morphology. In comparison to the Water/METH animals, the Sugar/METH animals demonstrated significant changes to a total of 102 proteins that were mainly involved in mitochondrial dysfunction and synaptic plasticity. Proteomic analyses identified a total of 74 differentially expressed proteins in the Sugar/METH condition compared to controls which were mainly critical in regulating cellular processes and molecular transport.