Cocaine-induced locomotor sensitization associates with slow oscillatory firing of neurons in the ventral tegmental area.

The initiation of psychostimulant sensitization depends on the mesocorticolimbic dopamine (DA) system. Although many cellular adaptations has been reported to be associated with this addictive behavior, the overall influence of these adaptations on the network regulation of DA neurons has not been established. Here, we profile a network-driven slow oscillation (SO) in the firing activity of ventral tegmental area (VTA) putative DA and non-DA neurons and their correlation with locomotor sensitization induced by repeated administration of cocaine. One day after the last cocaine injection, the power of SO (Pso) significantly increased both in DA and non-DA neurons. Interestingly, the Pso in DA neurons was positively correlated, while Pso in non-DA neurons was negatively correlated with the level of locomotor sensitization. On the other hand, the firing rates of DA and non-DA neurons were both elevated, but none exhibited any correlation with the level of sensitization. Fourteen days after the last injection, the Pso of DA neurons dissipated but still positively correlated with the level of sensitization. In contrast, the Pso in non-DA neurons lost correlation with locomotor sensitization. These results suggest that cocaine-induced locomotor sensitization is associated with long-term network adaptation in DA system and that DA and non-DA neurons may corporately facilitate/hamper the initiation of locomotor sensitization.