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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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Reduction of spontaneous exploratory activity in the open field test after clonidine treatment.A, Schematic representation (obtained from MUX_XYZ16L software) of the accumulated movement performed during 10 minutes for control (left) and clonidine-treated (CLO, right) mice on the box surface. B, Evolution of the accumulated activity during the 10-minute test, showing the maintained reduced activity of clonidine-treated mice. C, Percentage of total time spent in the inner quadrant in 5 and 10 inutes for control group (white bar) and CLO group (black bar). N = 21∶21.
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pone-0114869-g004: Reduction of spontaneous exploratory activity in the open field test after clonidine treatment.A, Schematic representation (obtained from MUX_XYZ16L software) of the accumulated movement performed during 10 minutes for control (left) and clonidine-treated (CLO, right) mice on the box surface. B, Evolution of the accumulated activity during the 10-minute test, showing the maintained reduced activity of clonidine-treated mice. C, Percentage of total time spent in the inner quadrant in 5 and 10 inutes for control group (white bar) and CLO group (black bar). N = 21∶21.

Mentions: At 5 min., exploratory activity of the control group was greater than that of the clonidine-treated group (2156.57±68.52 units vs. 914.29±109.25 xy ray cuts, p<0.001). At 10 minutes, the exploratory capacity remained higher for the control group (3735.81±134.37 xy ray cuts) than for the clonidine-treated group (1625.14±195.25 xy ray cuts, p<0.001) (Fig. 4A-B). In general, exploratory activity was greater for the Control mice than for the clonidine-treated group (F(5,36) = 91.442; p<0.001).


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

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

Reduction of spontaneous exploratory activity in the open field test after clonidine treatment.A, Schematic representation (obtained from MUX_XYZ16L software) of the accumulated movement performed during 10 minutes for control (left) and clonidine-treated (CLO, right) mice on the box surface. B, Evolution of the accumulated activity during the 10-minute test, showing the maintained reduced activity of clonidine-treated mice. C, Percentage of total time spent in the inner quadrant in 5 and 10 inutes for control group (white bar) and CLO group (black bar). N = 21∶21.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0114869-g004: Reduction of spontaneous exploratory activity in the open field test after clonidine treatment.A, Schematic representation (obtained from MUX_XYZ16L software) of the accumulated movement performed during 10 minutes for control (left) and clonidine-treated (CLO, right) mice on the box surface. B, Evolution of the accumulated activity during the 10-minute test, showing the maintained reduced activity of clonidine-treated mice. C, Percentage of total time spent in the inner quadrant in 5 and 10 inutes for control group (white bar) and CLO group (black bar). N = 21∶21.
Mentions: At 5 min., exploratory activity of the control group was greater than that of the clonidine-treated group (2156.57±68.52 units vs. 914.29±109.25 xy ray cuts, p<0.001). At 10 minutes, the exploratory capacity remained higher for the control group (3735.81±134.37 xy ray cuts) than for the clonidine-treated group (1625.14±195.25 xy ray cuts, p<0.001) (Fig. 4A-B). In general, exploratory activity was greater for the Control mice than for the clonidine-treated group (F(5,36) = 91.442; p<0.001).

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