Individual Differences in Amphetamine Locomotor Sensitization are Accompanied with Changes in Dopamine Release and...

Not all the people that consume drugs of abuse develop addiction. In this sense, just a percentage of rats express locomotor sensitization after repeated psychostimulant exposure. Neurochemical evidence has shown that locomotor sensitization is associated with changes in dorsolateral striatum (DLS) activity. However, it is unknown if individual differences observed in locomotor sensitization are related to differential neuro-adaptations in DLS activity. In this study, we measured basal dopamine (DA) levels and single unit activity in the DLS of anesthetized rats, after repeated amphetamine (AMPH) administration. Rats were treated with AMPH 1.0 mg/kg ip or saline ip for 5 days. Following 5 days of withdrawal, a challenge dose of AMPH 1.0 mg/kg ip was injected. In-vivo microdialysis experiments and single unit recording were carried out twenty-four hours after the last AMPH injection. Sensitized rats showed increased basal DA levels and baseline firing rate of medium spiny neurons (MSNs) compared to non-sensitized rats. The local variation index (Lv) was used to measure the firing pattern of MSNs. In saline rats, a bursty firing pattern was observed in MSNs. A decrease in MSNs baseline Lv accompanies the expression of AMPH locomotor sensitization. Moreover, a decrease in Lv after an acute AMPH 1.0 mg/kg injection was only observed in saline and sensitized rats. Our results show individual differences in DLS basal DA levels and firing pattern after repeated AMPH administration, suggesting that an hyperfunction of nigrostriatal pathway, accompanied by a decrease in DLS MSNs firing irregularity underlies the expression of AMPH locomotor sensitization.