PMID- 16442781 OWN - NLM STAT- MEDLINE DCOM- 20060712 LR - 20220310 IS - 0920-9964 (Print) IS - 0920-9964 (Linking) VI - 82 IP - 1 DP - 2006 Feb 15 TI - Differential effects of long-term treatment with typical and atypical antipsychotics on NGF and BDNF levels in rat striatum and hippocampus. PG - 95-106 AB - The results of mostly short-term treatment studies in human patients and animals suggest that second-generation antipsychotics (SGAs) such as risperidone (RISP) and olanzapine (OLZ) compared to first-generation antipsychotics (FGAs) such as haloperidol (HAL) and chlorpromazine (CPZ) have neuroprotective effects. The animal studies indicate that these effects are probably mediated through increased expression of neurotrophic factors such as nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF). However, since antipsychotics are commonly used for very long-term treatment periods, particularly in schizophrenic patients, it is important to measure the effects of chronic administration of antipsychotic drugs on the aforementioned growth factors. This study determined the effects of 90- and 180-day treatments with two FGAs, HAL and CPZ, and two SGAs, RISP and OLZ, on the levels of NGF and BDNF protein in hippocampus and striatum of rat. Furthermore, since a preliminary study showed that 90-day treatment of HAL caused significant reductions in the expression of both NGF and BDNF the HAL-treated animals were then switched to SGAs for the next 90 days to assess the potential for restoration of trophic factor levels. After the 90-day treatment, NGF levels in the hippocampus were reduced by 60-70% with HAL or CPZ, and by only 25-30% with RISP or OLZ compared to levels with vehicle only. After the 180-day treatment, NGF levels were further reduced with HAL, RISP, and OLZ, but not with CPZ. The magnitude of the NGF decreases in the striatum was larger (70-90%) with all the antipsychotics compared to the hippocampus. However, the pattern of BDNF changes in the hippocampus differed significantly from the striatum after 90- or 180-day treatment with the antipsychotics. In hippocampus, compared to controls, BDNF levels remained unchanged with OLZ both after 90 and 180 days of treatment. Whereas, larger decreases in BDNF levels were observed with HAL or CPZ and intermediate decreases were observed with RISP after 90 days of treatment that continued to decline up to 180 days. Furthermore, switching HAL animals after 90 days of treatment to either RISP or OLZ for the next 90 days significantly restored levels of both NGF and BDNF in both the brain regions. These data indicate that SGAs compared to FGAs induce less deleterious effects on neurotrophic factor levels in the brain and may also offer ability to reverse the more pronounced negative effects of FGAs as well. These data may have significant clinical implications for long-term antipsychotic selection as well as the common practice of antipsychotic switchover. FAU - Pillai, Anilkumar AU - Pillai A AD - Psychiatry and Health Behavior, Medical College of Georgia, Augusta, GA, USA. apillai@mail.mcg.edu FAU - Terry, Alvin V Jr AU - Terry AV Jr FAU - Mahadik, Sahebarao P AU - Mahadik SP LA - eng GR - MH 066233/MH/NIMH NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20060125 PL - Netherlands TA - Schizophr Res JT - Schizophrenia research JID - 8804207 RN - 0 (Antipsychotic Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 12794-10-4 (Benzodiazepines) RN - 9061-61-4 (Nerve Growth Factor) RN - J6292F8L3D (Haloperidol) RN - L6UH7ZF8HC (Risperidone) RN - N7U69T4SZR (Olanzapine) RN - U42B7VYA4P (Chlorpromazine) SB - IM MH - Animals MH - Antipsychotic Agents/*adverse effects MH - Benzodiazepines/adverse effects MH - Brain-Derived Neurotrophic Factor/*drug effects MH - Chlorpromazine/adverse effects MH - Corpus Striatum/*drug effects MH - Haloperidol/adverse effects MH - Hippocampus/*drug effects MH - Male MH - Nerve Growth Factor/*drug effects MH - Olanzapine MH - Rats MH - Rats, Wistar MH - Risperidone/adverse effects MH - Time EDAT- 2006/01/31 09:00 MHDA- 2006/07/13 09:00 CRDT- 2006/01/31 09:00 PHST- 2005/08/02 00:00 [received] PHST- 2005/11/22 00:00 [revised] PHST- 2005/11/30 00:00 [accepted] PHST- 2006/01/31 09:00 [pubmed] PHST- 2006/07/13 09:00 [medline] PHST- 2006/01/31 09:00 [entrez] AID - S0920-9964(05)00525-6 [pii] AID - 10.1016/j.schres.2005.11.021 [doi] PST - ppublish SO - Schizophr Res. 2006 Feb 15;82(1):95-106. doi: 10.1016/j.schres.2005.11.021. Epub 2006 Jan 25.