Effects of a neurosteroid, pregnenolone, during the neonatal period on adenosine A1 receptor, dopamine metabolites in the fronto-parietal cortex and behavioral response in the open field

• Published in: Brain research 2002-11, Vol.956 (2), p.332-338
• Main Authors: MUNEOKA, Katsumasa T, SHIRAYAMA, Yukihiko, MINABE, Yoshio, TAKIGAWA, Morikuni
• Format: Article
• Language: English
• Subjects: 3,4-Dihydroxyphenylacetic Acid - metabolism; Animals; Animals, Newborn; Behavior, Animal - drug effects; Behavioral psychophysiology; Biological and medical sciences; Chromatography, High Pressure Liquid; Dopamine - metabolism; Female; Frontal Lobe - drug effects; Frontal Lobe - metabolism; Fundamental and applied biological sciences. Psychology; Homovanillic Acid - metabolism; Hydroxyindoleacetic Acid - metabolism; Male; Neurotransmission and behavior; Parietal Lobe - drug effects; Parietal Lobe - metabolism; Pregnenolone - administration & dosage; Pregnenolone - metabolism; Pregnenolone - pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P1 - drug effects; Receptors, Purinergic P1 - metabolism; Serotonin - metabolism
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/s0006-8993(02)03567-9

Neuronal dysfunction in the frontal cortex has been reported in the etiology of mental disorders, including schizophrenia. The adenosine A(1) receptor system, as well as the dopaminergic system, are important in the control of cortical neuronal activity. We hypothesize that neuroexcitability in early life is critical to the normal development of the brain, and neurosteroids are factors that modulate neuroexcitability during the development period. In this study, we treated neonatal rats with a neurosteroid, pregnenolone (10 microg/g) from postnatal day (PD) 3 until PD 7. In pregnenolone-treated male and female rats, adenosine A(1) receptor density, the amount of dopamine (DA), serotonin (5-HT) and their metabolites in the fronto-parietal cortex and behavioral responses in the open field were examined pre- and post-puberty. A decrease in K(d) values for the adenosine A(1) receptor binding assay using [(3)H]1,3-dipropyl-8-cyclopentylxanthine (DPCPX), increased formation of DA metabolites and hyper-locomotor activity in the open field were found in pregnenolone-treated rats compared with controls in pre- and post-puberty. An increase in 5-HT metabolites was found in the pregnenolone-treated rats in pre-puberty, but not post-puberty. These effects of pregnenolone were not different between males and females. However, correlations between horizontal and vertical activities in the open field were disrupted only in pregnenolone-treated females. The present results indicate that pregnenolone treatment during the neonatal period influences the cortical dopaminergic and adenosinergic systems as well as behavioral responses in the open field.