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Clonidine treatment delays postnatal motor development and blocks short-term memory in young mice.

Calvino-Núñez C, Domínguez-del-Toro E - PLoS ONE (2014)

Bottom Line: It's especially important to look for the early neurological consequences resulting from such modifications, because they may go unnoticed.The main objective of the present study has been to reaffirm the importance of the maturation of alpha-adrenergic system in mice, by carrying out a comprehensive examination of motor, behavioral and cognitive effects in neonates, during early postnatal development, following chronic administration of the drug Clonidine, an alpha2 adrenergic system agonist.Shortly after the treatment the startle response is hyperreactive.

View Article: PubMed Central - PubMed

Affiliation: División de Neurociencias, Universidad Pablo de Olavide, Sevilla, Spain.

ABSTRACT
During the development of the nervous system, the perinatal period is particularly sensitive as neuronal connections are still forming in the brain of the neonate. Alpha2-adrenergic receptors are overexpressed temporarily in proliferative zones in the developing brain, reaching a peak during the first postnatal week of life. Both stimulation and blocking of these receptors during this period alter the development of neural circuits, affecting synaptic connectivity and neuronal responses. They even affect motor and cognitive skills later on in the adult. It's especially important to look for the early neurological consequences resulting from such modifications, because they may go unnoticed. The main objective of the present study has been to reaffirm the importance of the maturation of alpha-adrenergic system in mice, by carrying out a comprehensive examination of motor, behavioral and cognitive effects in neonates, during early postnatal development, following chronic administration of the drug Clonidine, an alpha2 adrenergic system agonist. Our study shows that mice treated postnatally with clonidine present a temporal delay in the appearance of developmental markers, a slow execution of vestibular reflexes during first postnatal week of life and a blockade of the short term memory in the novel object recognition task. Shortly after the treatment the startle response is hyperreactive.

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Effects of clonidine treatment during novel object recognition (NOR) memory test in mice.A, Recognition Index. The CLO-treated group (CLO) presents no increase in the Recognition Index [TB/(TA+TB)] for the short-term retention test (STM) and the long-term one (LTM), compared with the increase normally observed in control subjects. B, Total contacts with both objects. The CLO-treated group presents, during the training session (T), a significantly reduced object exploration. There is no reduction of object exploration in the short-term memory test for this group, but there is for the long-term memory test. C, Escape attempt. During training and short-term memory tests, the CLO-treated group presents almost no tendency to escape as compared with controls. This activity is increased in the long-term memory test, but results are significantly reduced as compared with the control group. Results are presented as means±S.E.M. The statistically significant difference between the two groups is represented by the symbol *, while the symbol # is used to compare the different tests—short- and long-term retention—with training. N = 40∶40.
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pone-0114869-g005: Effects of clonidine treatment during novel object recognition (NOR) memory test in mice.A, Recognition Index. The CLO-treated group (CLO) presents no increase in the Recognition Index [TB/(TA+TB)] for the short-term retention test (STM) and the long-term one (LTM), compared with the increase normally observed in control subjects. B, Total contacts with both objects. The CLO-treated group presents, during the training session (T), a significantly reduced object exploration. There is no reduction of object exploration in the short-term memory test for this group, but there is for the long-term memory test. C, Escape attempt. During training and short-term memory tests, the CLO-treated group presents almost no tendency to escape as compared with controls. This activity is increased in the long-term memory test, but results are significantly reduced as compared with the control group. Results are presented as means±S.E.M. The statistically significant difference between the two groups is represented by the symbol *, while the symbol # is used to compare the different tests—short- and long-term retention—with training. N = 40∶40.

Mentions: Using the novel object recognition (NOR) task, we could evaluate short-term (1 h) and long-term (24 h) memory of young mice when they are exposed to new and familiar objects. In this task, for the control group the Recognition Index increased to 0.57±0.01 in the short-term retention test, while the clonidine-treated group kept the same value as in training (0.48±0.03), indicating that the clonidine-treated group had no preference for either object (p = 0.002). At 24 h the indices remained at the same values than at the training test (0.49±0.02 vs. 0.50±0.03; p = 0.702) (Fig. 5A).


Clonidine treatment delays postnatal motor development and blocks short-term memory in young mice.

Calvino-Núñez C, Domínguez-del-Toro E - PLoS ONE (2014)

Effects of clonidine treatment during novel object recognition (NOR) memory test in mice.A, Recognition Index. The CLO-treated group (CLO) presents no increase in the Recognition Index [TB/(TA+TB)] for the short-term retention test (STM) and the long-term one (LTM), compared with the increase normally observed in control subjects. B, Total contacts with both objects. The CLO-treated group presents, during the training session (T), a significantly reduced object exploration. There is no reduction of object exploration in the short-term memory test for this group, but there is for the long-term memory test. C, Escape attempt. During training and short-term memory tests, the CLO-treated group presents almost no tendency to escape as compared with controls. This activity is increased in the long-term memory test, but results are significantly reduced as compared with the control group. Results are presented as means±S.E.M. The statistically significant difference between the two groups is represented by the symbol *, while the symbol # is used to compare the different tests—short- and long-term retention—with training. N = 40∶40.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4273991&req=5

pone-0114869-g005: Effects of clonidine treatment during novel object recognition (NOR) memory test in mice.A, Recognition Index. The CLO-treated group (CLO) presents no increase in the Recognition Index [TB/(TA+TB)] for the short-term retention test (STM) and the long-term one (LTM), compared with the increase normally observed in control subjects. B, Total contacts with both objects. The CLO-treated group presents, during the training session (T), a significantly reduced object exploration. There is no reduction of object exploration in the short-term memory test for this group, but there is for the long-term memory test. C, Escape attempt. During training and short-term memory tests, the CLO-treated group presents almost no tendency to escape as compared with controls. This activity is increased in the long-term memory test, but results are significantly reduced as compared with the control group. Results are presented as means±S.E.M. The statistically significant difference between the two groups is represented by the symbol *, while the symbol # is used to compare the different tests—short- and long-term retention—with training. N = 40∶40.
Mentions: Using the novel object recognition (NOR) task, we could evaluate short-term (1 h) and long-term (24 h) memory of young mice when they are exposed to new and familiar objects. In this task, for the control group the Recognition Index increased to 0.57±0.01 in the short-term retention test, while the clonidine-treated group kept the same value as in training (0.48±0.03), indicating that the clonidine-treated group had no preference for either object (p = 0.002). At 24 h the indices remained at the same values than at the training test (0.49±0.02 vs. 0.50±0.03; p = 0.702) (Fig. 5A).

Bottom Line: It's especially important to look for the early neurological consequences resulting from such modifications, because they may go unnoticed.The main objective of the present study has been to reaffirm the importance of the maturation of alpha-adrenergic system in mice, by carrying out a comprehensive examination of motor, behavioral and cognitive effects in neonates, during early postnatal development, following chronic administration of the drug Clonidine, an alpha2 adrenergic system agonist.Shortly after the treatment the startle response is hyperreactive.

View Article: PubMed Central - PubMed

Affiliation: División de Neurociencias, Universidad Pablo de Olavide, Sevilla, Spain.

ABSTRACT
During the development of the nervous system, the perinatal period is particularly sensitive as neuronal connections are still forming in the brain of the neonate. Alpha2-adrenergic receptors are overexpressed temporarily in proliferative zones in the developing brain, reaching a peak during the first postnatal week of life. Both stimulation and blocking of these receptors during this period alter the development of neural circuits, affecting synaptic connectivity and neuronal responses. They even affect motor and cognitive skills later on in the adult. It's especially important to look for the early neurological consequences resulting from such modifications, because they may go unnoticed. The main objective of the present study has been to reaffirm the importance of the maturation of alpha-adrenergic system in mice, by carrying out a comprehensive examination of motor, behavioral and cognitive effects in neonates, during early postnatal development, following chronic administration of the drug Clonidine, an alpha2 adrenergic system agonist. Our study shows that mice treated postnatally with clonidine present a temporal delay in the appearance of developmental markers, a slow execution of vestibular reflexes during first postnatal week of life and a blockade of the short term memory in the novel object recognition task. Shortly after the treatment the startle response is hyperreactive.

Show MeSH
Related in: MedlinePlus