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Consequences of early postnatal benzodiazepines exposure in rats. I. Cognitive-like behavior.

Mikulecká A, Subrt M, Stuchlík A, Kubová H - Front Behav Neurosci (2014)

Bottom Line: Between-session habituation, however, was found only in the controls.No difference between groups was found in a repeated acquisition test (10 and 40 days after the first acquisition test).Not only were changes observed on conventional cognitive tests in our study, but the changes also seem to be related to emotional/motivational responsiveness.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic Prague, Czech Republic.

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.

No MeSH data available.


Related in: MedlinePlus

Design/time diagram of CZP experimental procedure. The upper part shows a timeline for behavioral tests such as homing response (HR), habituation, and the Morris water maze (MWM) after exposure to 0.5 and 1.0 mg/kg/day of CZP between P7 and P11. The lower part shows a timeline for passive avoidance after exposure to 1.0 mg/kg/day of CZP.
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Figure 1: Design/time diagram of CZP experimental procedure. The upper part shows a timeline for behavioral tests such as homing response (HR), habituation, and the Morris water maze (MWM) after exposure to 0.5 and 1.0 mg/kg/day of CZP between P7 and P11. The lower part shows a timeline for passive avoidance after exposure to 1.0 mg/kg/day of CZP.

Mentions: Behavioral tests were performed in a special room with constant temperature (22 ± 2°C) and light conditions (35–45 lx). Before testing, animals were allowed to adapt to the testing room for 30 min. All tests were performed between 9:00 AM and 3:00 PM. The detailed experimental schedule is summarized in Figure 1. The same animals (controls n = 12; CZP 0.5 mg/kg/day, n = 12; CZP 1.0 mg/kg/day, n = 16) were used for the homing test, the habituation test and the MWM test, and the order of tests was always the same (homing test → habituation test → MWM). An additional 120 animals were used for the passive avoidance test. For each age group tested (P12, P15, P18, P25, P32), naïve animals were always used (controls n = 12; CZP 1.0 mg/kg/day, n = 12). The control group and the group exposed to CZP at the dose of 1.0 mg/kg each consisted of 12 animals. Behaviors in the OF and on the MWM were video-recorded and then analyzed using EthoVision (Noldus Information Technology).


Consequences of early postnatal benzodiazepines exposure in rats. I. Cognitive-like behavior.

Mikulecká A, Subrt M, Stuchlík A, Kubová H - Front Behav Neurosci (2014)

Design/time diagram of CZP experimental procedure. The upper part shows a timeline for behavioral tests such as homing response (HR), habituation, and the Morris water maze (MWM) after exposure to 0.5 and 1.0 mg/kg/day of CZP between P7 and P11. The lower part shows a timeline for passive avoidance after exposure to 1.0 mg/kg/day of CZP.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3975106&req=5

Figure 1: Design/time diagram of CZP experimental procedure. The upper part shows a timeline for behavioral tests such as homing response (HR), habituation, and the Morris water maze (MWM) after exposure to 0.5 and 1.0 mg/kg/day of CZP between P7 and P11. The lower part shows a timeline for passive avoidance after exposure to 1.0 mg/kg/day of CZP.
Mentions: Behavioral tests were performed in a special room with constant temperature (22 ± 2°C) and light conditions (35–45 lx). Before testing, animals were allowed to adapt to the testing room for 30 min. All tests were performed between 9:00 AM and 3:00 PM. The detailed experimental schedule is summarized in Figure 1. The same animals (controls n = 12; CZP 0.5 mg/kg/day, n = 12; CZP 1.0 mg/kg/day, n = 16) were used for the homing test, the habituation test and the MWM test, and the order of tests was always the same (homing test → habituation test → MWM). An additional 120 animals were used for the passive avoidance test. For each age group tested (P12, P15, P18, P25, P32), naïve animals were always used (controls n = 12; CZP 1.0 mg/kg/day, n = 12). The control group and the group exposed to CZP at the dose of 1.0 mg/kg each consisted of 12 animals. Behaviors in the OF and on the MWM were video-recorded and then analyzed using EthoVision (Noldus Information Technology).

Bottom Line: Between-session habituation, however, was found only in the controls.No difference between groups was found in a repeated acquisition test (10 and 40 days after the first acquisition test).Not only were changes observed on conventional cognitive tests in our study, but the changes also seem to be related to emotional/motivational responsiveness.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physiology, Academy of Sciences of the Czech Republic Prague, Czech Republic.

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.

No MeSH data available.


Related in: MedlinePlus