Locomotor sensitization, defined as the progressive and enduring enhancement of the motor stimulant effects elicited by repeated exposure to drugs of abuse, is the consequence of drug-induced cellular neuroadaptations that likely contribute to addictive behavior.
Neuroadaptations within the dopaminergic system have been shown to be involved both in the induction phase and in the long-term expression phase of sensitization upon drug readministration after withdrawal.
In spite of the absence of the DAT, mutant mice were able to develop long-term expression of sensitization to cocaine. Compared to their wild-type littermates, DAT-KO mice exhibited a markedly increased acute ethanol-evoked locomotor activity and developed stronger behavioral sensitization to ethanol during both induction and long-term expression phases. Interestingly, this increased ethanol-induced sensitization was potentiated by the DBA/2 genetic background.
These findings, showing that DAT deletion facilitates sensitization, suggest a cross-sensitization-like effect between genetic- and pharmacological-induced hyperdopaminergia.
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