Elsevier

Neuroscience

Volume 81, Issue 1, 26 August 1997, Pages 129-140
Neuroscience

Prenatal corticosterone treatment induces long-term changes in spontaneous and apomorphine-mediated motor activity in male and female rats

https://doi.org/10.1016/S0306-4522(97)00141-3Get rights and content

Abstract

The potential influence of glucocorticoids on fetal brain development was investigated after corticosterone administration via pellets to pregnant rats during the last trimester of gestation. We examined both spontaneous motor activity and dopamine-mediated motor responses to apomorphine, a predominantly D1 and D2 receptor agonist, given at a postsynaptic dose (1 mg/kg, s.c.) to both prepubertal and adult male and female offspring. Prenatal corticosterone was found to produce the following alterations in the offspring: (1) Prepubertal stage: Male offspring: A statistically significant (P<0.05) increase was observed in spontaneous rearing, motility and locomotion (activity measured during the first 30 min) without changes in apomorphine-induced motor responses. Female offspring: A reduction (P<0.05) only in spontaneous rearing activity was observed during the exploratory phase (activity measured during the first 10 min) without significant changes in apomorphine-induced motor responses. (2) Adult stage: Male offspring: The exploratory activity to the novel environment was increased (P<0.05) without significant changes in apomorphine-induced motor activity. Female offspring: An increase (P<0.05) in spontaneous locomotion was observed during the first 30 min of testing without significant changes in exploratory activity to the novel environment. However, the apomorphine-induced motility and locomotion were reduced (P<0.05) during the first 30 min.

These observations indicate that prenatal corticosterone induces both short-term and long-term changes in spontaneous motor activity as well as long-lasting alterations in dopamine receptor response in the motor network mechanisms controlled by DA receptors. These changes are in part age and sex-dependent. The possible relationship between prenatal programming of the mesolimbic and nigrostriatal dopaminergic pathways by corticosterone and the observed changes in motor function is discussed.

Section snippets

Animals

Thirty nulliparus pregnant Sprague–Dawley rats (300 g body weight) with a defined day of fertilization were obtained from B and K (Sollentuna, Sweden). Birth normally occurs on day 22 of gestation. On the day of arrival (day 12 of pregnancy), the animals were housed individually in type IV Macrolon® and randomly assigned to placebo or corticosterone groups. They were kept in a temperature- and humidity-controlled room under a regular day and night cycle (lights on at 06.00 and off at 18.00) with

Plasma corticosterone levels in the dams

On the morning of delivery, we found plasma corticosterone levels of 4.1±1 μg/100 ml (means±S.E.M.) in the placebo-treated group (n=6) and 9.9±1.6 μg/100 ml in the corticosterone-treated (n=3) rats maintained under minimal stress conditions. Thus, the corticosterone pellets used doubled (P<0.05) the amount of morning plasma corticosterone levels in the dams.

Characterization of the behavioural model

The experimental model consisted of two recording periods: (i) recording of spontaneous motor activity (60 min) and (ii) recording of drug

Discussion

The aim of the present study was to investigate the effects of prenatal corticosterone exposure on a functional postsynaptic DA receptor response in both prepubertal and adult male and female rats. The model consisted of a continuous administration of corticosterone via a pellet implanted in the pregnant dam during the last trimester of gestation. The corticosterone pellet used raises maternal plasma corticosterone to levels comparable to the ones observed during mild stress (for further

Conclusions

In summary, continuous exposure to corticosterone (leading to a two fold increase in plasma corticosterone) via pellets to pregnant dams resulted in sex-dependent alterations in spontaneous and apomorphine-induced motor activity in prepubertal and adult offspring. The apomorphine results may suggest long-lasting reductions in DA receptor sensitivity and/or in the cellular/and motor network mechanisms controlled by DA receptors that are in part age and sex-dependent. The effects of prenatal

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