Increased immunoreactivity of POMC-derived neuropeptides and immediate-early gene-derived proteins (c-Fos and Egr-1 proteins) as an early step of acute cocaine-induced stressor effects: comparison with the effects of immobilization stress.
The effects of an acute toxic dose of cocaine (COC) (60 mg/kg, i.p.) as a stressor were examined in rats both neuroendocrinally and behaviorally. The time course (5 min, 5, 12, and 24 h) of the alterations in the immunoreactivity of POMC (preopiomelanocortin)-derived neuropeptides [ACTH (adrenocorticotropin), beta-endorphin, and alpha-MSH (melanocyte stimulating hormone)] and immediate-early gene-derived proteins (c-fos and egr-1 proteins) was examined in the hypothalamus, including the regions reported to be neuroendocrinally sensitive to stressor effects, along with the accompanying alterations in the spontaneous behaviors in the cage and the forced swimming behaviors. Similar to the observations in rats treated with a 30 min immobilization stress (IM), an increase in the number of immunoreactive nerve cells for each neuroendocrinal product and a delayed depression in the swimming behaviors as compared to the alterations in the spontaneous activity, which seemed to be correlated with some intermediate steps, were characteristically caused by a toxic dose of COC. However, the early enhancement (at 5 h) of the swimming behaviors and the brain ACTH level might also be the characteristic acute COC effects, which could be differentiated from the effects of other non-psychostimulant stressors.
Hayase
Tamaki
T
Department of Legal Medicine, Kyoto University Graduate School of Medicine, Faculty of Medicine, Kyoto 606-8501, Japan.
Yamamoto
Yoshiko
Y
Yamamoto
Keiichi
K
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D003042:Cocaine / Q000009:adverse effects*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007103:Immobilization / Q000009:adverse effects*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000209:etiology* / Q000378:metabolism* / Q000523:psychology; D014157:Transcription Factors / Q000378:metabolism*; D000521:alpha-MSH / Q000378:metabolism*; D001615:beta-Endorphin / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D000521:alpha-MSH; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D003042:Cocaine