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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

Effect of CZP exposure (1.0 mg/kg) on passive avoidance retention performance. The animals were tested at P12, P15, P18, P25 and at P32. Abscissae: the 1st, the 2nd and the 3rd trials. Ordinate: time of entry latencies in seconds. * Significant differences compared to an appropriate control group; # significant difference between sessions.
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Figure 4: Effect of CZP exposure (1.0 mg/kg) on passive avoidance retention performance. The animals were tested at P12, P15, P18, P25 and at P32. Abscissae: the 1st, the 2nd and the 3rd trials. Ordinate: time of entry latencies in seconds. * Significant differences compared to an appropriate control group; # significant difference between sessions.

Mentions: In the first trial, step-through latency decreased with maturation. In the retention trials, performed at 2 h and at 24 h, the latency increased continuously as a function of age, indicating the development of avoidance memory. CZP did not affect this developmental trend (p < 0.001 for both controls and CZP-exposed animals). Criteria set for full retention was achieved at P25 in both the controls and the CZP-exposed animals (p < 0.001). Passive avoidance response was not present in P12 rats in any trial, and CZP had no effect. In the first trial, the CZP-exposed animals tested at P15, P18, and P25 displayed shorter step-through latencies than the controls. This suggested that all CZP animals reacted differently than the controls to a new environment, with low exploration of the light box and suppressed risk-assessment behavior (animals enter the dark box without hesitation), whereas control animals demonstrated caution and risk-assessment behavior before walking into the dark box. This behavior was not observed in P32 animals. In P15, the step-through latency increase was observed only at 24 h after the first trial in both control and CZP-exposed rats [F(2.44) = 21.9, p < 0.001]. Starting at P18, the step-through latency significantly increased in both retention trials, that is, 2 and 24 h after the first trial [F(2,44) = 55.9, p < 0.001; F(2,44) = 289.4, p < 0.001; F(2,44) = 342.2, p < 0.001, respectively]. There was no difference between the controls and the CZP animals, suggesting that CZP exposure did not impair the retention of memory avoidance (Figure 4).


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

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

Effect of CZP exposure (1.0 mg/kg) on passive avoidance retention performance. The animals were tested at P12, P15, P18, P25 and at P32. Abscissae: the 1st, the 2nd and the 3rd trials. Ordinate: time of entry latencies in seconds. * Significant differences compared to an appropriate control group; # significant difference between sessions.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Effect of CZP exposure (1.0 mg/kg) on passive avoidance retention performance. The animals were tested at P12, P15, P18, P25 and at P32. Abscissae: the 1st, the 2nd and the 3rd trials. Ordinate: time of entry latencies in seconds. * Significant differences compared to an appropriate control group; # significant difference between sessions.
Mentions: In the first trial, step-through latency decreased with maturation. In the retention trials, performed at 2 h and at 24 h, the latency increased continuously as a function of age, indicating the development of avoidance memory. CZP did not affect this developmental trend (p < 0.001 for both controls and CZP-exposed animals). Criteria set for full retention was achieved at P25 in both the controls and the CZP-exposed animals (p < 0.001). Passive avoidance response was not present in P12 rats in any trial, and CZP had no effect. In the first trial, the CZP-exposed animals tested at P15, P18, and P25 displayed shorter step-through latencies than the controls. This suggested that all CZP animals reacted differently than the controls to a new environment, with low exploration of the light box and suppressed risk-assessment behavior (animals enter the dark box without hesitation), whereas control animals demonstrated caution and risk-assessment behavior before walking into the dark box. This behavior was not observed in P32 animals. In P15, the step-through latency increase was observed only at 24 h after the first trial in both control and CZP-exposed rats [F(2.44) = 21.9, p < 0.001]. Starting at P18, the step-through latency significantly increased in both retention trials, that is, 2 and 24 h after the first trial [F(2,44) = 55.9, p < 0.001; F(2,44) = 289.4, p < 0.001; F(2,44) = 342.2, p < 0.001, respectively]. There was no difference between the controls and the CZP animals, suggesting that CZP exposure did not impair the retention of memory avoidance (Figure 4).

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