LI is the reduced efficacy of a previously non-reinforced stimulu

LI is the reduced efficacy of a previously non-reinforced stimulus to gain behavioral control when paired with reinforcement, compared with a novel stimulus. Here, no-drug controls displayed LI if non-reinforced pre-exposure to a tone was followed by weak but not strong conditioning (2 vs 5 tone-shock

pairings). MK801 (0.05 mg/kg, i.p.)-treated rats as well as rats neonatally treated with nitric oxide synthase inhibitor L-NoArg (10 mg/kg, s.c.) on postnatal days 4-5, persisted in displaying LI with strong conditioning, whereas amphetamine (1 mg/kg) -treated rats failed to show LI with weak conditioning. SSR180711 (0.3, 1, 3 mg/kg, i.p.) was able to alleviate abnormally persistent LI produced by acute MK801 and neonatal L-NoArg; these models are believed to model cognitive aspects of schizophrenia and activity here was consistent with previous findings with alpha 7-nAChR agonists. In addition, unexpectedly, SSR180711 (1, 3 mg/kg, i.p.) potentiated LI with strong conditioning in no-drug controls and reversed amphetamine-induced LI disruption, two effects considered predictive of activity against positive symptoms of schizophrenia. These findings suggest that SSR180711 may be beneficial not only for the

treatment of cognitive symptoms in schizophrenia, as reported multiple times previously, but also positive symptoms. selleck kinase inhibitor Neuropsychopharmacology (2009) 34, 1753-1763; doi:10.1038/npp.2008.232; published online 21 January second 2009″

administration of antidepressant drugs produce changes in neuroplasticity and behavior in rodents, effects that may be associated with the slow emergence of clinical therapeutic effects. Owing to the uncertainty over the effects of chronic antidepressant treatments in mice, these experiments compared the regulation of neurogenesis, neurotrophin levels, and behavior produced by chronic antidepressant treatments between two inbred mouse strains, MRL/MpJ and C57BL/6J. The MRL/MpJ strain is associated with enhanced wound healing and tissue regeneration, whereas C57BL/6J mice are used commonly for behavioral studies. Proliferation and survival of hippocampal progenitor cells were measured using flow cytometry, a new platform that rapidly quantifies the incorporation of 5-bromo2-deoxyuridine (BrdU). Hippocampal cell proliferation was increased significantly after chronic administration of fluoxetine (FLX: 5, 10 mg/kg, intraperitoneal (i.p.), b.i.d.) or desipramine (DMI: 5, 10 mg/kg, i.p., b.i.d.) for 21 days in MRL/MpJ mice, but not in C57BL/6J mice. Hippocampal progenitor cells born prior to chronic antidepressant treatments were not affected in either mouse strain.

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