Hyperactivity and alteration of the midbrain dopaminergic system in maternally stressed male mice offspring

doi:10.1016/j.bbrc.2006.11.104

Biochemical and Biophysical Research Communications

Volume 352, Issue 3, 19 January 2007, Pages 823-829

https://doi.org/10.1016/j.bbrc.2006.11.104 Get rights and content

Abstract

We recently demonstrated that prolonged maternal stress produces profound and long-lasting deficits in brain functions by programming a subset of target genes. We have now examined the possible effects of prenatal stress on the motility of adult offspring and dopamine (DA)-related gene expression in their midbrains, one of the target brain regions of stress hormones. Maternally stressed adult male mice showed impaired response habituation to novelty, and increased wheel-running activity associated with altered responses to DA receptor and DA transporter (DAT) blockers. Along with the behavioral changes, the expression profiles of several genes of the midbrain DAergic system appeared to be altered. Expression of DAT was reduced and expression of DA receptors and striatal DA-regulated neuropeptide genes was also affected. Taken together, the present findings indicate that maternal stress can cause hyperactivity in adult offspring associated with alterations in the midbrain DAergic system suggestive of a functional hyperdopaminergic state.

Section snippets

Materials and methods

Maternal stress procedure and tissue preparation. ICR mice from the Laboratory Animal Center at Seoul National University were used in all experiments and kept in temperature-controlled (22–23 °C) quarters under a 12-h light and dark photoperiod (light on at 7:00 a.m.); standard mouse chow and water were available ad libitum. The maternal stress procedure has been described previously [2], [3]. Briefly, pregnant ICR mice were prepared by mating at the age of 6–7 weeks. Mice in the stress group

Results

To test whether prolonged maternal stress affects the motor activity of adult mice offspring, we adopted two experimental paradigms. These were response habituation in a novel environment and wheel-running activity in the home cage, both of which are known to depend on the midbrain DAergic system [10], [11], [14]. In the first experiment, measuring motility in a novel environment, both groups of mice had similar initial beam-breaking latencies. However, in the control mice these increased

Discussion

The present study was undertaken to determine whether prolonged maternal stress influences motor behavior and the midbrain DAergic system of adult mice offspring by modulating relevant gene expression. We employed two behavioral paradigms: motor responses to a novel environment and wheel-running activities in the home cage. In combination with these behavioral experiments, analysis of gene expression revealed, for the first time, that DAT and DA receptors are molecular targets implicated in the

Acknowledgments

This work was supported by a grant from the Korea Ministry of Science and Technology through the Brain Research Center of the 21st Century Frontier Research Program. G.H. Son and S. Chung were supported by Brain Korea 21 Research Fellowships from the Korea Ministry of Education.

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Hyperactivity and alteration of the midbrain dopaminergic system in maternally stressed male mice offspring

Abstract

Section snippets

Materials and methods

Results

Discussion

Acknowledgments

Neuroscience

Neuroscience

Prog. Neurobiol.

Pharmacol. Biochem. Behav.

Biol. Psychiatry

Behav. Brain Res.

Brain Res.

Brain Res.

Eur. J. Pharmacol.

Trends Neurosci.

Neuroscience

Exp. Neurol.

Brain Res.

Biol. Psychiatry

J. Am. Acad. Child Adolesc. Psychiatry

Prenatal stress, glucocorticoids and the programming of the brain

J. Neuroendocrinol.

Differential adaptive responses to chronic stress of maternally stressed male mice offspring

Endocrinology