Protracted effects of chronic oral @entity1767 and @entity1090 on XXXX , cholinergic neurons, and spatial reference learning in @entity35 .

@entity2137 @entity3249 @entity934 @entity161 @entity716 @entity1767 @entity35 @entity1090
The primary therapeutic agents used for @entity161 , antipsychotic drugs, ameliorate @entity716 symptoms; however, their chronic effects on cognition (or the physiologic processes of the brain that support cognition) are largely unknown. The purpose of this rodent study was to extend our previous work on this subject by investigating persistent effects (i.e. during a 14 day drug-free washout period) of chronic treatment (i.e. ranging from 45 days to 6 months) with a representative first and second generation antipsychotic. Drug effects on learning and memory and important neurobiological substrates of memory, the neurotrophin, @entity2137 ( @entity2137 ) and its receptors, and certain components of the basal forebrain cholinergic system were investigated. Behavioral effects of oral @entity1767 (2.0 mg/kg/day), or @entity1090 (2.5 mg/kg/day) were assessed in an open field, a water maze task, and a radial arm maze procedure and neurochemical effects in brain tissue were subsequently measured by enzyme-linked immunosorbent assays (ELISAs). The results indicated that both antipsychotics produced time-dependent and protracted deficits in the performance of a water maze procedure when compared with vehicle-treated controls, while neither drug was associated with significant alterations in radial arm maze performance. Interestingly, @entity1767 , but not @entity1090 , was detectible in the rodent brain in appreciable levels for up to 2 weeks after drug discontinuation. Both antipsychotics were also associated with reduced levels of @entity2137 protein in the basal forebrain and prefrontal cortex and significant (or nearly significant) decreases in phosphorylated @entity3249 ( @entity3249 ) protein and the vesicular @entity934 transporter (depending on the brain region analyzed). Neither antipsychotic markedly affected @entity3249 or p75 neurotrophin receptor levels. These data in @entity35 indicate that chronic treatment with either @entity1767 or @entity1090 may be associated with protracted negative effects on cognitive function as well as important neurotrophin and neurotransmitter pathways that support cognition.
