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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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Effect of clonidine treatment on startle reflex parameters at different sound intensities.A, Latencies (in ms) until the appearance of the motor response reduce as intensity increases (75, 85, 95, 105, 115 and 125 dB), mainly at higher intensities. No differences are observed between control and clonidine-treated mice, apart from the case of the lowest intensity (75 dB). B, Area (in mN x s) of the increase in startle response with the intensity of the sound. Clonidine-treated mice show larger areas at intensities above 95 dB than control mice. N = 35∶35. * significant differences between control and clonidine (CLO) -treated mice, when p<0.05.
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pone-0114869-g002: Effect of clonidine treatment on startle reflex parameters at different sound intensities.A, Latencies (in ms) until the appearance of the motor response reduce as intensity increases (75, 85, 95, 105, 115 and 125 dB), mainly at higher intensities. No differences are observed between control and clonidine-treated mice, apart from the case of the lowest intensity (75 dB). B, Area (in mN x s) of the increase in startle response with the intensity of the sound. Clonidine-treated mice show larger areas at intensities above 95 dB than control mice. N = 35∶35. * significant differences between control and clonidine (CLO) -treated mice, when p<0.05.

Mentions: The other analyzed variable is Response area, obtained from the curve represented by the force exerted by the mouse on the surface during the acoustic stimulus (mNew x s). For this variable, we can see that from 95 dB on, the Response area for clonidine-treated mice is much greater than for controls, and its pattern remains almost parallel. In both groups of mice, Response area tends to increase with the sound intensity. At 95 dB and 105 dB intensities, the results reached statistical significance (p = 0.022 and p = 0.008) (Fig. 2).


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

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

Effect of clonidine treatment on startle reflex parameters at different sound intensities.A, Latencies (in ms) until the appearance of the motor response reduce as intensity increases (75, 85, 95, 105, 115 and 125 dB), mainly at higher intensities. No differences are observed between control and clonidine-treated mice, apart from the case of the lowest intensity (75 dB). B, Area (in mN x s) of the increase in startle response with the intensity of the sound. Clonidine-treated mice show larger areas at intensities above 95 dB than control mice. N = 35∶35. * significant differences between control and clonidine (CLO) -treated mice, when p<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0114869-g002: Effect of clonidine treatment on startle reflex parameters at different sound intensities.A, Latencies (in ms) until the appearance of the motor response reduce as intensity increases (75, 85, 95, 105, 115 and 125 dB), mainly at higher intensities. No differences are observed between control and clonidine-treated mice, apart from the case of the lowest intensity (75 dB). B, Area (in mN x s) of the increase in startle response with the intensity of the sound. Clonidine-treated mice show larger areas at intensities above 95 dB than control mice. N = 35∶35. * significant differences between control and clonidine (CLO) -treated mice, when p<0.05.
Mentions: The other analyzed variable is Response area, obtained from the curve represented by the force exerted by the mouse on the surface during the acoustic stimulus (mNew x s). For this variable, we can see that from 95 dB on, the Response area for clonidine-treated mice is much greater than for controls, and its pattern remains almost parallel. In both groups of mice, Response area tends to increase with the sound intensity. At 95 dB and 105 dB intensities, the results reached statistical significance (p = 0.022 and p = 0.008) (Fig. 2).

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