Effect of insulin deficiency on the rewarding properties of methamphetamine in streptozotocin-induced diabetic rats

• Methamphetamine dose-dependently produced place preference in the rats.
• Rewarding properties of methamphetamine changed in streptozotocin-induced diabetic rats.
• Insulin replacement improved the rewarding properties of methamphetamine.

The reward is a positive behavioural response to the pleasant stimuli that can be induced by drugs, such as psychostimulants. Furthermore, diabetes mellitus is a chronic disease that many people throughout the world suffer from. Methamphetamine (METH), as a psychostimulant, engages the dopaminergic system in the reward circuitry and the synapses of dopaminergic terminals can be modified by insulin. In this study, in order to assess the effect of insulin deficiency on reward, streptozotocin (STZ)-induced diabetic animals were used as an appropriate model. One hundred and thirty-two adult male rats were divided into nine groups (three non-diabetic and six diabetic groups) to determine the most effective dose of METH (0.25, 0.5, 1 and 2 mg/kg ip), and insulin replacement (10 U/kg; ip) during the acquisition period in a conditioned place preference (CPP) paradigm. The diabetes model was induced by a single injection of STZ (60 mg/kg; ip). The conditioning score was considered to be the difference in time spent in drug- and saline-paired compartments. The results demonstrated that the most effective doses of METH were 1 and 2 mg/kg in non-diabetic animals. Although the place preference was not shown in non-diabetic animals at the dose of 0.5 mg/kg, this dose significantly induced place preference to METH in STZ-diabetic rats. Additionally, insulin replacement could reverse the METH-induced CPP in diabetic animals. Our findings suggest that the positive effect of insulin deficiency on METH rewarding properties is dependent on insulin level in part, and the replacement of the insulin in diabetic rats as a treatment can improve the rewarding properties of METH.