Various studies suggest a dysfunction of nicotinic neurotransmission in
schizophrenia and establish that patients suffering from
schizophrenia and
attention deficit hyperactivity disorder (
ADHD) have a high tobacco consumption, potentially for the purpose of
self-medication. Owing to its neuroprotective and procognitive effects, transdermal
nicotine was proposed to be an effective treatment of some neurodegenerative and
psychiatric diseases. Mice deficient in the
dopamine transporter (DAT KO) exhibit a phenotype reminiscent of
schizophrenia and
ADHD, including hyperdopaminergia, hyperactivity, paradoxical calming by
methylphenidate and cognitive deficits, some of which being improved by
antipsychotic agents. We recently demonstrated that
nicotinic receptor content and function were profoundly modified in DAT KO mice. In this study, we assessed the effects of a chronic
nicotine treatment in the
drinking water on the
nicotine-induced locomotion, anxiety status and learning performance. Chronically
nicotine-treated DAT KO mice were always hypersensitive to the hypolocomotor effect of
nicotine without tolerance and did not exhibit the anxiogenic effect of
nicotine treatment observed in WT mice. Very interestingly, both acute and chronic
nicotine treatments greatly improved their deficits in the cued and spatial learning, without eliciting tolerance. We speculate that the procognitive effects of
nicotine in DAT KO mice are related to the upregulation of alpha7
nicotinic receptors in the hippocampus, amygdala, and prelimbic cortex, all areas involved in cognition. Data from our studies on DAT KO mice shed light on the
nicotine self-medication in psychiatric patients and suggest that
nicotinic agonists could favorably lead to additional
therapy of
psychiatric diseases.