Intermittent treatment with haloperidol or quetiapine does not disrupt motor and cognitive recovery after experimental brain trauma.
Traumatic brain injury (TBI)-induced agitation and aggression pose major obstacles to clinicians in the acute hospital and rehabilitation settings. Thus, management of these symptoms is crucial. Antipsychotic drugs (APDs) are a common treatment approach for alleviating these symptoms. However, previous preclinical TBI studies have indicated that daily and chronic administration of these drugs (e.g., haloperidol; HAL) can exacerbate cognitive and motor deficits. Quetiapine (QUE) is an atypical APD that differs from many typical APDs, such as HAL, in its relatively rapid dissociation from the D2receptor. The goal of this study was to test the hypotheses that intermittent HAL and QUE would not hinder recovery of cognitive and motor function following TBI and that daily QUE would also not impair functional recovery, which would be in contrast to HAL. Seventy anesthetized male rats received either a controlled cortical impact or sham injury and were then randomly assigned to TBI and sham groups receiving HAL (0.5mg/kg) or QUE (10mg/kg) intraperitoneally once per day or once every other day and compared to each other and vehicle (VEH) controls. Motor function was assessed by beam balance/walk tests on post-operative days 1-5 and cognitive function was evaluated with a Morris water maze task on days 14-19. No differences were revealed among the sham groups in any task, and hence the data were pooled. No overall differences were detected among the TBI groups, regardless of treatment or administration paradigm [p>0.05], but all were impaired vs. SHAM controls [p<0.05]. The SHAM controls also performed significantly better in the cognitive test vs. all TBI groups [p<0.05]. Moreover, the TBI+continuous HAL group performed worse than the TBI+continuous VEH, TBI+continuous QUE, and TBI+intermittent QUE groups [p<0.05], which did not differ from one another. Overall, the data suggest that QUE does not exacerbate TBI-induced cognitive and motor deficits, which supports the hypothesis. QUE may prove useful as an alternative APD treatment for management of agitation and aggression after clinical TBI. HAL may also be safe, but only if used sparingly.
Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15213, United States.
Jillian J
JJ
Weeks
Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, 15213, United States.
Lauren J
LJ
Carlson
Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, 15213, United States.
Hannah L
HL
Radabaugh
Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, 15213, United States.
Patricia B
PB
de la Tremblaye
Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Neurobiology, University of Pittsburgh, Pittsburgh, PA, 15213, United States.
Corina O
CO
Bondi
Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Psychology, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, 15213, United States. Electronic address: klineae@upmc.edu.
Anthony E
AE
Kline
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology*; D003071:Cognition / Q000187:drug effects*; D004334:Drug Administration Schedule; D006220:Haloperidol / Q000008:administration & dosage*; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D000069348:Quetiapine Fumarate / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D065852:Spatial Memory / Q000187:drug effects
D014150:Antipsychotic Agents; D000069348:Quetiapine Fumarate; D006220:Haloperidol
Antipsychotic drugs; Behavioral outcome; Controlled cortical impact; Functional recovery; Learning and memory; Morris water maze; Traumatic brain injury
Brain Res. 2002 Nov 29;956(2):349-57
12445705
Neurosci Lett. 2008 Dec 31;448(3):263-7
18983891
Prog Neuropsychopharmacol Biol Psychiatry. 2002 Oct;26(6):1047-54
12452525
Neurorehabil Neural Repair. 2011 May;25(4):343-50
21186330
J Head Trauma Rehabil. 2008 Mar-Apr;23 (2):132-5
18362767
Brain Res. 2016 Jun 1;1640(Pt A):5-14
26612522
Semin Neurol. 2015 Feb;35(1):64-82
25714869
J Psychiatry Neurosci. 2000 Mar;25(2):161-6
10740989
Neurosci Biobehav Rev. 2015 Nov;58:123-46
25496906
Am J Phys Med Rehabil. 2005 Oct;84(10):797-812
16205436
J Neurosci Methods. 1984 May;11(1):47-60
6471907
Behav Brain Res. 2006 Sep 15;172(1):39-45
16712969
Am J Phys Med Rehabil. 2003 Nov;82(11):871-9
14566156
Arch Phys Med Rehabil. 1996 Jun;77(6):617-23
8831483
J Clin Psychiatry. 2008 Mar;69(3):497-8
18402501
Prog Neurobiol. 2016 Jul;142:45-67
27166858
Neuropsychopharmacology. 2001 Nov;25(5):633-41
11682246
J Integr Neurosci. 2014 Dec;13(4):669-92
25391717
Neurosci Lett. 2000 Feb 25;280(3):163-6
10675786
Brain Res. 2015 Oct 5;1622:443-51
26188240
Proc West Pharmacol Soc. 1985;28:209-11
4070250
Restor Neurol Neurosci. 1999;14(4):285-294
12671249
Crit Care Med. 2007 Mar;35(3):919-24
17255872
Brain Inj. 2012;26(9):1155-62
22642404
J Neurotrauma. 2002 Apr;19(4):415-25
11990348
Neurorehabil Neural Repair. 2011 Jul-Aug;25(6):558-64
21436387
Eur Psychiatry. 2013 Mar;28(3):174-84
22153730
Science. 1982 Aug 27;217(4562):855-7
7100929
J Neurotrauma. 2014 May 15;31(10):873-88
24555571
J Rehabil Res Dev. 2009;46(6):851-79
20104408
J Neurotrauma. 2010 Nov;27(11):2021-32
21028935
Arch Gen Psychiatry. 2000 Jun;57(6):553-9
10839333
J Neurotrauma. 2017 Jan 15;34(2):444-450
26972895
J Neurotrauma. 2004 Dec;21(12):1712-22
15684763
J Psychiatr Res. 1998 May-Aug;32(3-4):215-28
9793875
J Neurotrauma. 2012 Nov 20;29(17):2684-8
22774771
Mol Psychiatry. 2005 Jan;10(1):79-104
15289815
J Neurotrauma. 2017 Jan 15;34(2):451-458
26975872
J Neuropsychiatry Clin Neurosci. 2006 Fall;18(4):547-9
17135382
Life Sci. 2008 Oct 24;83(17-18):602-7
18801378
J Neurotrauma. 2015 Apr 15;32(8):590-7
25275833
Psychopharmacology (Berl). 2012 Mar;220(1):65-74
21918808
J Head Trauma Rehabil. 2008 Mar-Apr;23(2):123-31
18362766
Neurorehabil Neural Repair. 2002 Dec;16(4):321-5
12462763
Brain Inj. 1997 May;11(5):335-41
9146839
Front Psychiatry. 2012 Sep 14;3:82
23049514
J Head Trauma Rehabil. 1999 Dec;14(6):602-15
10671706
Physiol Res. 2010;59(2):263-71
19537923