Differential effects of long-term treatment with typical and atypical antipsychotics on NGF and BDNF levels in rat striatum and hippocampus

Psychiatry and Health Behavior, Medical College of Georgia, Augusta, GA, USA.
Schizophrenia Research (Impact Factor: 4.43). 03/2006; 82(1):95-106. DOI: 10.1016/j.schres.2005.11.021
Source: PubMed

ABSTRACT 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.

  • Source
    Neuropsychiatric Disease and Treatment 04/2015; · 2.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We evaluated anti-Parkinson's activity of methanolic extract of Juniperus communis (MEJC) leaves in chlorpromazine (CPZ) induced experimental animal model. In this study effects of Juniperus communis (100 and 200 mg/kg, i.p.) were studied using various behavior parameters like catalepsy (bar test), muscle rigidity (rotarod test), and locomotor activity (actophotometer) and its effect on neurochemical parameters (TBARS, GSH, nitrite, and total protein) in rats. The experiment was designed, by giving chlorpromazine (3 mg/kg, i.p.) for 21 days to induce Parkinson's disease-like symptoms. Chlorpromazine significantly induced motor dysfunctions (catalepsy, muscle rigidity, and hypolocomotion) in a period of 21 days. The MEJC significantly (í µí±ƒ < 0.001) reduced catalepsy and muscle rigidity and significantly (í µí±ƒ < 0.001) increased locomotor activity in rats. The maximum reduction was observed on the 21st day at a dose of 200 mg/kg (i.p.). The MEJC extract also showed an increase in the level of reduced gutathione (GSH) (í µí±ƒ < 0.001) and total protein (í µí±ƒ < 0.001) and decreased the elevated levels of TBARS (í µí±ƒ < 0.001) and nitrite (í µí±ƒ < 0.001) preferably at a higher dose (200 mg/kg) as compared to chlorpromazine group. Thus the present study showed the neuroprotective effect of MEJC against CPZ induced Parkinson's disease-like symptoms or anti-Parkinson's activity.
    International Scholarly Research Notices 09/2014; 2014:6. DOI:10.1155/2015/542542
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Since its discovery several decades ago, nerve growth factor (NGF) has been found to play roles in different areas, such as neurology, endocrinology, and immunology. There is some evidence linking NGF and psychiatry, including the role of NGF in subjects' response to stress, the alteration of NGF in different emotional states, and the penetration of NGF across the blood-brain barrier under specific conditions. There are many inconsistent findings regarding the differences in NGF in patients with major depressive disorder (MDD) at the present time. The aim of our study was to clarify whether NGF levels are different in MDD compared with healthy controls (HCs). We conducted a thorough literature search and compared peripheral NGF levels between MDD and HC through meta-analysis, and investigated possible confounding variables through meta-regression. Seven studies were brought into the current meta-analysis comparing peripheral NGF in MDD and HCs. The main result was that the NGF levels were significantly lower in MDD than in HCs and that this had an inverse correlation with mean age and disease severity. In addition, meta-analysis of four articles found that the peripheral NGF levels did not change significantly before and after treatment. Our study highlights the significant differences in peripheral NGF levels in patients with MDD. However, further exploration of the dynamic changes in peripheral NGF along with the disease course, and specific studies investigating the correlation of NGF in the peripheral and CNS environments are still needed.
    Neuropsychiatric Disease and Treatment 01/2015; 11:925-33. DOI:10.2147/NDT.S81432 · 2.15 Impact Factor