Haloperidol, but Not Olanzapine, Impairs Cognitive Performance After Traumatic Brain Injury in Rats

Wilson, Margaret S.; Gibson, Cynthia J.; Hamm, Robert J.

doi:10.1097/01.phm.0000091982.33232.cb

Cited by 79 publications

(83 citation statements)

References 20 publications

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“…Support for this notion derives from previous work in our laboratory demonstrating that the D 2 -receptor antagonist haloperidol impedes the ability of rats to successfully navigate a water maze task to find the escape platform Kline et al, 2007aKline et al, ,2008. Water maze performance is also impaired by haloperidol in a fluid percussion model of TBI (Wilson et al, 2003). Taken together, these TBI studies from independent laboratories indicate that D 2 -receptor antagonism impairs cognitive outcome.…”

Section: Discussionsupporting

confidence: 53%

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT_1A-Receptor Agonist Buspirone

Olsen

Sozda

Cheng

et al. 2012

Journal of Neurotrauma

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The aim of this study was to evaluate the potential efficacy of the serotonin 1A (5-HT 1A ) receptor agonist buspirone (BUS) on behavioral and histological outcome after traumatic brain injury (TBI). Ninety-six isofluraneanesthetized adult male rats were randomized to receive either a controlled cortical impact or sham injury, and then assigned to six TBI and six sham groups receiving one of five doses of BUS (0.01, 0.05, 0.1, 0.3, or 0.5 mg/kg) or saline vehicle (VEH, 1.0 mL/kg). Treatments began 24 h after surgery and were administered intraperitoneally once daily for 3 weeks. Motor function (beam-balance/beam-walk tests) and spatial learning/memory (Morris water maze) were assessed on post-operative days 1-5 and 14-19, respectively. Morphologically intact CA1/ CA3 cells and cortical lesion volume were quantified at 3 weeks. No differences were observed among the BUS and VEH sham groups in any end-point measure and thus the data were pooled. Regarding the TBI groups, repeated-measures ANOVAs revealed that the 0.3 mg/kg dose of BUS enhanced cognitive performance relative to VEH and the other BUS doses ( p < 0.05), but did not significantly impact motor function. Moreover, the same dose conferred selective histological protection as evidenced by smaller cortical lesions, but not greater CA1/ CA3 cell survival. No significant behavioral or histological differences were observed among the other BUS doses versus VEH. These data indicate that BUS has a narrow therapeutic dose response, and that 0.3 mg/kg is optimal for enhancing spatial learning and memory in this model of TBI. BUS may have potential as a novel pharmacotherapy for clinical TBI.

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Section: Discussionsupporting

confidence: 53%

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT_1A-Receptor Agonist Buspirone

Olsen

Sozda

Cheng

et al. 2012

Journal of Neurotrauma

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“…However, the effect of atypical antipsychotics on cognition is not well established in the population with TBI. In rat models, multiple administration of olanzapine did not impair cognitive function, as did haloperidol [115]. Another rat study showed deterioration of motor and cognitive performance after multiple administrations of both haloperidol and high-dose risperidone [116].…”

Section: Neurolepticsmentioning

confidence: 99%

Pharmacological management of neurobehavioral disorders following traumatic brain injuryA state-of the-art review

Chew

Zafonte²

2009

JRRD

163

103

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Abstract-Pharmacological management of neurobehavioral disorders following traumatic brain injury (TBI) is common practice. However, the evidence available to guide this practice remains sparse. This review summarizes, in brief, the state of knowledge, organized via a time continuum from injury as well as by symptom complex. The areas of neuroprotection, hypoarousal, attention and memory deficits, aggression, agitation, depression, and mania are reviewed. The literature was searched with PubMed on the terms "traumatic brain injury" or "brain injury" with "pharmacology" (and the symptoms according to which this review is arranged). Additional searches were conducted with the specific symptoms as search terms, crossed with the therapeutic agents or drug classes discussed. Where a paucity of prospective data exists, case reports and retrospective studies are included. Studies to date have yielded minimal positive evidence for enhancing function, memory, and behavior after TBI. No single agent likely will become sentinel in the recovery process, and combination therapy in the acute and postacute settings are required. A need exists to further define the role of psychopharmacology in postacute TBI medicine and the specific characteristics of subpopulations who might benefit.

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“…Further support for this hypothesis stems from work showing that olanzapine, a third-generation APD with less-robust DA activity, did not negatively impact cognitive performance. 13 …”

Section: Phelps Et Almentioning

confidence: 99%

“…12 Aside from deleterious effects on motor performance, daily HAL treatment (15 days) after fluid percussion injury significantly delayed the acquisition of spatial learning in the Morris water maze (MWM), compared to injury alone. 13 In controlled cortical impact (CCI) injury studies, both HAL and RISP delayed motor and cognitive recovery when administered chronically and concomitantly with behavioral testing. [14][15][16] Moreover, both HAL and RISP reinstated motor and cognitive deficits in rats that appeared to be fully recovered, and the cognitive impairments lasted for at least 3 days after discontinuation of treatment.…”

Section: Introductionmentioning

confidence: 99%

Divergent Long-Term Consequences of Chronic Treatment with Haloperidol, Risperidone, and Bromocriptine on Traumatic Brain Injury–Induced Cognitive Deficits

Phelps

Bondi

Ahmed

et al. 2015

Journal of Neurotrauma

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Antipsychotic drugs (APDs) are provided in the clinic to manage traumatic brain injury (TBI)-induced agitation and aggression. Experimental TBI studies consistently show that daily administration of the APDs, haloperidol (HAL) and risperidone (RISP), hinder recovery. However, it is unknown how long the adverse effects remain after cessation of treatment. To elucidate this clinically relevant issue, anesthetized male rats were randomly assigned to four TBI (controlled cortical impact) and four sham groups administered HAL (0.5 mg/kg), RISP (0.45 mg/kg), bromocriptine (BRO; 5.0 mg/kg, included as a control for D 2 receptor action), or vehicle (VEH; 1 mL/kg) 24 h after surgery and once-daily for 19 days. Motor and cognitive recovery was assessed on days 1-5 and 14-19, respectively, and again at 1 and 3 months after drug withdrawal. No overall group differences were observed for motor function among the TBI groups, although the HAL group showed a greater beam-walk deficit on day 5 versus the VEH and BRO groups. Cognitive recovery was significantly impaired in the HAL and RISP groups during the treatment phase versus VEH and BRO. Further, BRO was superior to VEH ( p = 0.0042). At 1 month, both groups that received APDs continued to exhibit significant cognitive impairment versus VEH and BRO; at 3 months, only the HAL group was impaired. Moreover, the HAL, RISP, and VEH groups continued to be cognitively deficient versus BRO, which also reduced cortical damage. These data replicate previous reports that HAL and RISP impede cognitive recovery after TBI and expand the literature by revealing that the deleterious effects persist for 3 months after drug discontinuation. BRO conferred cognitive benefits when administered concomitantly with behavioral testing, thus replicating previous findings, and also after cessation demonstrating enduring efficacy.

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Haloperidol, but Not Olanzapine, Impairs Cognitive Performance After Traumatic Brain Injury in Rats

Cited by 79 publications

References 20 publications

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT_1A-Receptor Agonist Buspirone

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT_1A-Receptor Agonist Buspirone

Pharmacological management of neurobehavioral disorders following traumatic brain injuryA state-of the-art review

Divergent Long-Term Consequences of Chronic Treatment with Haloperidol, Risperidone, and Bromocriptine on Traumatic Brain Injury–Induced Cognitive Deficits

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Haloperidol, but Not Olanzapine, Impairs Cognitive Performance After Traumatic Brain Injury in Rats

Cited by 79 publications

References 20 publications

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT1A-Receptor Agonist Buspirone

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT1A-Receptor Agonist Buspirone

Pharmacological management of neurobehavioral disorders following traumatic brain injuryA state-of the-art review

Divergent Long-Term Consequences of Chronic Treatment with Haloperidol, Risperidone, and Bromocriptine on Traumatic Brain Injury–Induced Cognitive Deficits

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Product

Resources

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Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT_1A-Receptor Agonist Buspirone

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT_1A-Receptor Agonist Buspirone