Age-specific effects of 6-hydroxydopamine lesions of the rat medial  prefrontal cortex on stress-induced c-fos expression in subcortical  areas.
As adolescence is a critical period when dopaminergic neuronal maturation peaks, we hypothesized that 6-hydroxydopamine (OHDA) lesions of the medial prefrontal cortex (mPFC) in adolescent rats would have more negative effects than lesions in adult rats. Therefore, we investigated the effects of 6-OHDA lesions of the mPFC in adolescent and adult rats on stress-induced c-fos expression in the brain. Adolescent and adult Sprague-Dawley rats, aged 4 and 7 weeks on arrival, respectively, were studied. 6-OHDA (8.0 microg) for the lesion groups and ascorbic acid for the sham groups were injected bilaterally into the mPFC. All animals were pretreated with desipramine 30 min before being anesthetized. The control group did not undergo any surgery-related procedure except the desipramine injection. After recovery for 1 week, the rats were subjected to restraint stress for 1 h. Immediately after the stress, the rats were killed and c-fos immunohistochemistry was examined. The c-fos expression in the nucleus accumbens core (AcbC), nucleus accumbens shell (AcbSh), CA1, CA3, dentate gyrus (DG), central amygdaloid (Ce), basolateral amygdaloid (BL), and temporal cortex (Tc) was compared. Adolescent rats with 6-OHDA lesions subjected to restraint stress had greater c-fos expression in the AcbC, AcbSh, DG, Ce, BL, and Tc, compared to the sham and control groups, whereas these differences were not observed among the adult groups. These results suggest that a hypodopaminergic state in the mPFC of adolescent rats, but not adult rats, is related to increased sensitivity to stress, suggesting that damage to or maldevelopment of dopaminergic neurons during adolescence has an age-specific effect. Further research is warranted to investigate the mechanism of the age-specific effect of 6-OHDA lesions of the mPFC.
Sui
Zhi Yan
ZY
Department of Psychiatry, Chonbuk National University Medical School and Institute for Medical Sciences, San 2-20 Geumam-dong, Deokjin-gu, Jeonju 561-756, South Korea.
Li
Chun-Rong
CR
Huang
Guang-Biao
GB
Kwon
Young-Bae
YB
Kim
Kee-Won
KW
Lee
Keon-Hak
KH
Chung
Young-Chul
YC
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000367:Age Factors; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013312:Stress, Physiological
D016760:Proto-Oncogene Proteins c-fos; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; D004298:Dopamine; D009638:Norepinephrine