Changes in the pattern of brain-derived neurotrophic factor immunoreactivity in the rat brain after acute and subchronic haloperidol treatment

Dawson, Niamh M.; Hamid, Emad H.; Egan, Michael; Meredith, Gloria E.

doi:10.1002/1098-2396(20010101)39:1<70::aid-syn10>3.0.co;2-j

Cited by 50 publications

(27 citation statements)

References 62 publications

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“…In contrast, other studies reported that both activation and inhibition of the DA system with, respectively, chronic cocaine (Fumagalli et al, 2007) and 6-OHDA treatment (Zhang et al, 2006) failed to affect striatal levels of BDNF. Furthermore, blockade of D 2 Rs with haloperidol treatment for 3 d (Dawson et al, 2001) or 90 d (Pillai et al, 2006) significantly reduced striatal BDNF, whereas intermediate time windows of haloperidol exposure (21 d) caused a partial rebound of striatal BDNF immunoreactivity (Pillai et al, 2006). Together, these data indicate that DA-dependent regulation of striatal BDNF is not unidirectional and that stimulatory effects are evident only in response to acute treatments.…”

Section: Discussionmentioning

confidence: 72%

Brain-Derived Neurotrophic Factor Controls Cannabinoid CB1 Receptor Function in the Striatum

Chiara¹,

Angelucci²,

Rossi³

et al. 2010

Journal of Neuroscience

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The role of brain-derived neurotrophic factor (BDNF) in emotional processes suggests an interaction with the endocannabinoid system. Here, we addressed the functional interplay between BDNF and cannabinoid CB 1 receptors (CB 1 Rs) in the striatum, a brain area in which both BDNF and CB 1 s play a role in the emotional consequences of stress and of rewarding experiences.BDNF potently inhibited CB 1 R function in the striatum, through a mechanism mediated by altered cholesterol metabolism and membrane lipid raft function. The effect of BDNF was restricted to CB 1 Rs controlling GABA-mediated IPSCs (CB 1 R (GABA) ), whereas CB 1 Rs modulating glutamate transmission and GABA B receptors were not affected. The action of BDNF on CB 1 R (GABA) function was tyrosine kinase dependent and was complete even after receptor sensitization with cocaine or environmental manipulations activating the dopamine (DA)-dependent reward system. In mice lacking one copy of the BDNF gene (BDNF The present study identifies a novel mechanism of CB 1 R regulation mediated by BDNF and cholesterol metabolism and provides some evidence that DA D 2 R-dependent modulation of striatal CB 1 R activity is mediated by this neurotrophin.

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Section: Discussionmentioning

confidence: 72%

Brain-Derived Neurotrophic Factor Controls Cannabinoid CB1 Receptor Function in the Striatum

Chiara¹,

Angelucci²,

Rossi³

et al. 2010

Journal of Neuroscience

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“…In the present study, we found prevention of the HAL-induced reduction in BDNF protein levels by rhEPO co-treatment. This co-treatment approach is, therefore, important since earlier studies from our own and other laboratories have shown that long-term (44 weeks) HAL treatment causes reduction in BDNF levels Angelucci et al, 2000;Dawson et al, 2001) and EPO levels in rat brain. The argument that the neuroprotective role of rhEPO against HAL-induced cell death (in our study) was likely mediated via its effects on BDNF was supported by the reduced cortical neuronal cell survival induced by a specific neutralizing BDNF antibody.…”

Section: Discussionmentioning

confidence: 99%

“…This dose is also comparable to the optimal dose to cause pharmacological effects (Skarsfeldt, 1996;Didriksen, 1995;Bymaster et al, 1996). The schedule of HAL administration was selected based on several studies by us and others in which differences in behavioral as well as pharmacological effects were seen after 45 days of treatment in rats (Parikh et al, 2004a, b, c;Terry et al, 2004;Pillai et al, 2005;Angelucci et al, 2000;Dawson et al, 2001). rhEPO (500 U/kg; Epoetin alfa, Eprex, Cilag) was administered intraperitoneally three times per week for 6 weeks.…”

Section: Drug Treatments In Ratsmentioning

confidence: 99%

Erythropoietin Prevents Haloperidol Treatment-Induced Neuronal Apoptosis through Regulation of BDNF

Pillai

Dhandapani

Pillai

et al. 2007

Neuropsychopharmacol

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Functional alterations in the neurotrophin, brain-derived neurotrophic factor (BDNF) have recently been implicated in the pathophysiology of schizophrenia. Furthermore, animal studies have indicated that several antipsychotic drugs have time-dependent (and differential) effects on BDNF levels in the brain. For example, our previous studies in rats indicated that chronic treatment with the conventional antipsychotic, haloperidol, was associated with decreases in BDNF (and other neurotrophins) in the brain as well as deficits in cognitive function (an especially important consideration for the therapeutics of schizophrenia). Additional studies indicate that haloperidol has other deleterious effects on the brain (eg increased apoptosis). Despite such limitations, haloperidol remains one of the more commonly prescribed antipsychotic agents worldwide due to its efficacy for the positive symptoms of schizophrenia and its low cost. Interestingly, the hematopoietic hormone, erythropoietin, in its recombinant human form rhEPO has been reported to increase the expression of BDNF in neuronal tissues and to have neuroprotective effects. Such observations provided the impetus for us to investigate in the present study whether co-treatment of rhEPO with haloperidol could sustain the normal levels of BDNF in vivo in rats and in vitro in cortical neuronal cultures and further, whether BDNF could prevent haloperidol-induced apoptosis through the regulation of key apoptotic/antiapoptotic markers. The results indicated that rhEPO prevented the haloperidol-induced reduction in BDNF in both in vivo and in vitro experimental conditions. The sustained levels of BDNF in rats with rhEPO prevented the haloperidol-induced increase in caspase-3 (po0.05) and decrease in Bcl-xl (po0.01) protein levels. Similarly, in vitro experiments showed that rhEPO prevented (po0.001) the haloperidol-induced neuronal cell death as well as the decrease in Bcl-xl levels (po0.01). These findings may have significant implications for the development of neuroprotective strategies to improve clinical outcomes when antipsychotic drugs are used chronically.

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“…Antidepressant treatments upregulate BDNF expression in the DG (Chen et al, 2001;Nibuya et al, 1995). In contrast, BDNF expression is reduced in the hippocampus of rats chronically treated with haloperidol or clozapine (Dawson et al, 2001;Lipska et al, 2001;ChlanFourney et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Effects of Chronic Haloperidol and Clozapine Treatment on Neurogenesis in the Adult Rat Hippocampus

Halim

Weickert

McClintock

et al. 2004

Neuropsychopharmacol

173

109

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It has been proposed that the therapeutic benefits of treatment with antidepressants and mood stabilizers may arise partially from their ability to stimulate neurogenesis. This study was designed to examine the effects of chronic antipsychotic treatment on cell proliferation and survival in the adult rat hippocampus. Haloperidol (0.05 and 2 mg/kg), clozapine (0.5 and 20 mg/kg), or vehicle were administered i.p. for 28 days, followed by bromodeoxyuridine (BrdU, 200 mg/kg, i.p.), a marker of DNA synthesis. One group of rats was killed 24 h following BrdU administration and BrdU-positive cells were quantified to assess the effects of drug treatment on cell proliferation. The remaining animals continued on antipsychotic medication for an additional 3 weeks following BrdU administration to assess the effects of antipsychotics on cell survival. Our results show that 24 h following BrdU, a low dose of clozapine (0.5 mg/kg) increased the number of BrdU-positive cells in the dentate gyrus (DG) by two-fold. Neither 20 mg/kg of clozapine nor haloperidol had any effect on cell proliferation in DG. Moreover, neither drug at either dose had an effect on the number of newly generated neurons surviving in the DG 3 weeks following BrdU administration. These preliminary findings suggest that clozapine may influence the number of cells which divide, but antipsychotics do not promote the survival of the newly generated neurons at 3 weeks after a BrdU injection.

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Changes in the pattern of brain-derived neurotrophic factor immunoreactivity in the rat brain after acute and subchronic haloperidol treatment

Cited by 50 publications

References 62 publications

Brain-Derived Neurotrophic Factor Controls Cannabinoid CB1 Receptor Function in the Striatum

Brain-Derived Neurotrophic Factor Controls Cannabinoid CB1 Receptor Function in the Striatum

Erythropoietin Prevents Haloperidol Treatment-Induced Neuronal Apoptosis through Regulation of BDNF

Effects of Chronic Haloperidol and Clozapine Treatment on Neurogenesis in the Adult Rat Hippocampus

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