Chronic antipsychotic treatment: protracted decreases in phospho-TrkA levels in the rat hippocampus

There is growing evidence of neurotrophin alterations in neuropsychiatric illnesses such as schizophrenia and further, neurotransmitters known to be adversely affected in schizophrenia (e.g. dopamine) can activate neurotrophin signalling pathways via G protein-coupled receptors. However, it is unclear how the primary therapeutic agents used in schizophrenia affect neurotrophin signalling. This is important given that all currently prescribed antipsychotic drugs serve as ligands at dopamine receptors. In this study, chronic effects of representative conventional and second-generation antipsychotics on nerve growth factor (NGF) receptor levels were assessed in the rat. The results indicated no significant drug effects on TrkA levels in any brain region analysed; however, three of the five antipsychotics analysed significantly decreased phospho-TrkA (i.e. the activated form of the receptor) in the hippocampus. These data indicate that chronic antipsychotic treatment may result in deleterious effects on neurotrophin signalling in an important brain region for information processing and cognition.