Abstract

Methylphenidate (MPD) is a psychostimulant that is widely prescribed to treat attention deficit-hyperactivity disorder, but it is abused recreationally as well. The nucleus accumbens (NAc) is part of the motivation circuit implicated in drug-seeking behaviors. The NAc neuronal activity was recorded alongside the behavioral activity from young and adult rats to determine if there are significant differences in the response to MPD. The same dose of MPD elicits behavioral sensitization in some animals and behavioral tolerance in others. In adult animals, higher doses of MPD resulted in a greater ratio of tolerance/sensitization. Animals who responded to chronic MPD with behavioral sensitization usually exhibited further increases in their NAc neuronal firing rates as well. Different upregulations of transcription factors (ΔFOSB/CREB), variable proportions of D1/D2 dopamine receptors, and modulation from other brain areas may predispose certain animals to express behavioral and neuronal sensitization versus tolerance to MPD.

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