An increased function in the mesolimbic dopaminergic system has been extensively associated with the rewarding effects of both natural stimuli and drugs of abuse. Thus,
dopamine receptor blockers, such as
neuroleptic drugs, can be proposed as candidates for potential therapeutic approaches to treat
drug dependence. Notwithstanding, this therapeutic potential of
neuroleptics critically depends on a selective action on the specific mechanisms related to the development of addiction. We compared the effects of different doses of
haloperidol,
ziprasidone and
aripiprazole (first-, second- and third-generation
neuroleptics, respectively) on spontaneous locomotor activity of mice in a novel environment, hyperlocomotion induced by acute
cocaine administration and
cocaine-induced locomotor sensitization by a two-injection protocol. Whereas high doses of
haloperidol abolished the three behavioural paradigms without selectivity, low doses of
ziprasidone selectively abolished the development of the behavioural sensitization phenomenon. Finally, low doses of
aripiprazole inhibited acute
cocaine-induced hyperlocomotion and behavioural sensitization without modifying spontaneous locomotor activity. Thus,
aripiprazole at lower doses was the most selective
antipsychotic drug concerning the inhibition of the development of behavioural sensitization to
cocaine. Because locomotor sensitization in rodents has been proposed to share
plastic mechanisms with
drug addiction in humans, our data provide relevant suggestions to the clinical practice.