title: Consequences of early postnatal benzodiazepines exposure in rats. I. Cognitive-like behavior.
abstract: Clinical and experimental studies suggest possible risks associated with the repeated administration of benzodiazepines (BZDs) during the prenatal or early postnatal period on further development and behavior. In the present study, we assess short- and long-term effects of early exposure to clonazepam (CZP) on cognitive tasks. CZP (0.5 or 1.0 mg/kg/day) was administered from postnatal day (P)7 until P11, and animals were exposed to the following behavioral tests at different developmental stages: (1) a homing response (HR) test, which exploits the motivation of a rat pup to reach its home nest, was administered on P12, P15, P18 and P23 rats; (2) passive avoidance was tested in three trials (at 0, 2 and 24 h intervals) on P12, P15, P18, P25 and P32 rats; (3) within- and between-session habituation was tested in an open field (OF) at P70; and (4) a long-term memory (LTM) version of the Morris water maze (MWM) was tested at P80. A 1.0 mg/kg dose of CZP extended latency in the HR and decreased the number of correct responses when tested at P12 and P23. In the first trial of the passive avoidance test, latency to enter a dark compartment was shorter in the CZP-exposed rats. Both treated and control animals older than P15 learned the passive-avoidance response at the same rate. Irrespective of the treatments, all adult animals showed within-session habituation. Between-session habituation, however, was found only in the controls. With respect to the MWM test, all animals learned to reach the platform, but animals exposed to higher doses of CZP spent more time swimming in the first acquisition test. No difference between groups was found in a repeated acquisition test (10 and 40 days after the first acquisition test). The results of the present study show that even short-term exposure to CZP alters behavioral responsiveness in pre-weaning, juvenile and adult animals. Not only were changes observed on conventional cognitive tests in our study, but the changes also seem to be related to emotional/motivational responsiveness.
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic Prague, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Mikulecká
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Subrt
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic Prague, Czech Republic.
authors.forename: Aleš
authors.initials: A
authors.lastname: Stuchlík
authors.affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic Prague, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Kubová
keywords: benzodiazepines; clonazepam; cognitive functions; development; rats
references.citation: Neurotoxicology. 2007 Sep;28(5):931-7
references.pmid: 17368774
references.citation: Neurobehav Toxicol Teratol. 1986 Sep-Oct;8(5):447-52
references.pmid: 3785507
references.citation: Epilepsy Behav. 2011 Jan;20(1):12-9
references.pmid: 21130691
references.citation: Eur J Pharmacol. 2009 Jun 10;612(1-3):48-53
references.pmid: 19356730
references.citation: J Neurosci Methods. 1984 May;11(1):47-60
references.pmid: 6471907
references.citation: Brain Res Bull. 1992 Nov;29(5):609-16
references.pmid: 1422858
references.citation: Neurosci Biobehav Rev. 1985 Spring;9(1):101-11
references.pmid: 2858075
references.citation: Early Hum Dev. 1979 Mar;3(1):79-83
references.pmid: 118862
references.citation: Brain Res Brain Res Rev. 2001 Aug;36(1):60-90
references.pmid: 11516773
references.citation: Neurosci Biobehav Rev. 2006;30(7):1045-64
references.pmid: 16774787
references.citation: Anim Behav. 1975 Nov;23(4):896-920
references.pmid: 1200422
references.citation: Behav Brain Res. 1996 Aug;78(2):121-9
references.pmid: 8864044
references.citation: J Pharmacol Exp Ther. 1996 Nov;279(2):803-12
references.pmid: 8930187
references.citation: Neurotoxicol Teratol. 1990 Sep-Oct;12(5):489-95
references.pmid: 2247037
references.citation: Int Clin Psychopharmacol. 2006 May;21(3):131-42
references.pmid: 16528135
references.citation: Dev Pharmacol Ther. 1990;15(1):21-5
references.pmid: 2242707
references.citation: Behav Brain Res. 1999 Aug;103(1):1-11
references.pmid: 10475159
references.citation: J Pharm Pharmacol. 1993 Sep;45(9):807-10
references.pmid: 7903369
references.citation: Brain Res. 1997 Aug 22;766(1-2):142-52
references.pmid: 9359597
references.citation: Eur J Neurosci. 2006 Mar;23(5):1255-68
references.pmid: 16553788
references.citation: Neuroreport. 2010 Apr 21;21(6):452-6
references.pmid: 20848732
references.citation: Behav Neurosci. 2003 Jun;117(3):412-25
references.pmid: 12802871
references.citation: Psychopharmacology (Berl). 1984;83(1):51-5
references.pmid: 6429700
references.citation: Neurobehav Toxicol Teratol. 1986 Sep-Oct;8(5):425-32
references.pmid: 3024040
references.citation: Behav Brain Res. 2009 Dec 1;204(1):133-9
references.pmid: 19505510
references.citation: Brain Res Brain Res Rev. 2003 Mar;41(2-3):268-87
references.pmid: 12663083
references.citation: Trends Neurosci. 2002 Oct;25(10):518-24
references.pmid: 12220880
references.citation: Neuroscience. 1999;93(1):243-51
references.pmid: 10430488
references.citation: Front Neural Circuits. 2012 Mar 01;6:8
references.pmid: 22403529
references.citation: An Acad Bras Cienc. 2000 Sep;72(3):353-64
references.pmid: 11028100
references.citation: Eur J Pharmacol. 2001 Nov 16;431(2):189-200
references.pmid: 11728425
references.citation: Dev Psychobiol. 1980 Jul;13(4):385-98
references.pmid: 7390019
references.citation: Addiction. 2011 Dec;106(12):2086-109
references.pmid: 21714826
references.citation: Arch Int Pharmacodyn Ther. 1989 May-Jun;299:35-43
references.pmid: 2774770
references.citation: Neurotoxicol Teratol. 1988 Mar-Apr;10(2):101-11
references.pmid: 2840561