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Background:  Inhalant (e.g. toluene) misuse by adolescents has been linked to psychosis and persistent cognitive deficits. Identifying effective strategies to improve cognitive deficits following chronic toluene misuse is critical. 5-HT 1A  receptor has been proposed as a target for the treatment of cognitive deficits. Objectives:  We compared the effects of antipsychotics on recognition deficits after adolescent toluene exposure in mice and elucidated the role of 5-HT 1A  receptors in the cognition-improving effects of antipsychotics. Methods:  Male NMRI mice (n = 279) received one injection per day of either toluene (750 mg/kg) or corn oil at postnatal days 35–39 and 42–46. Thereafter, the acute and subchronic effects of haloperidol, aripiprazole, or clozapine on toluene-induced recognition deficits were evaluated by novel object recognition test. Results:  Acute administration of aripiprazole ( p  &lt; .05) and clozapine ( p  &lt; .01), but not haloperidol, significantly attenuated the toluene-induced recognition deficits. Pretreatment with 5-HT 1A  receptor antagonist WAY -100,635 ( p  &lt; .05) blocked their beneficial effects. Moreover, 5-HT 1A  receptor agonist buspirone ( p  &lt; .01) ameliorated the toluene-induced recognition deficits, which was reversed by WAY -100,635 ( p  &lt; .001). Finally, after repeated treatment with clozapine, aripiprazole, and buspirone daily for 14 days, the impaired object recognition in toluene-exposed mice was significantly improved ( p  &lt; .05) and the beneficial effects lasted for at least 2 weeks ( p  &lt; .05). Conclusions:  The results indicate that clozapine and aripiprazole, which display 5-HT 1A  agonist properties, restored cognitive deficits in mice induced by adolescent toluene exposure. These findings suggest that these antipsychotics should be further explored as a potential treatment option for cognitive deficits in patients with psychosis associated with toluene exposure.

the american journal of drug and alcohol abuse

Beneficial effects of atypical antipsychotics on object recognition deficits after adolescent toluene exposure in mice: involvement of 5-HT 1A  receptors