Stressor-like effects of cocaine on heat shock protein and stress-activated protein kinase expression in the rat hippocampus: interaction with ethanol and anti-toxicity drugs.
The present study examined the stressor-like effects of repeated (4 days) administration of cocaine hydrochloride(COC) (35 mg/kg, i.p.) on the expression of heat shock proteins (HSPs) (HSP27, HSP60, HSP70, HSC70) and stress-activated protein kinases (SAPKs) (SAPKalpha, SAPKbeta, SAPKgamma) in the rat hippocampus. The interactions with intraperitoneal ethanol and drugs known as antidotes against COC toxicity were also examined. Similar to the effects of a 10 min immobilization stress (IM) over 4 days, an early increase (5 h time point) in nerve cells immunoreactive for HSPs (HSP27, HSP60, HSP70, HSC70) and SAPKs (SAPKbeta, SAPKgamma) was observed in the COC group. At the 24 h time point, a recovery was observed only for SAPKs, which have been suggested to control the HSP levels. Before the 48 h time point, alterations in the number of HSP+cells as compared to the control group (increase for HSP27 and HSP70+cells, and attenuation for HSP60 and HSC70+cells) could still be observed. Stress-related, attenuated swimming behaviors in the forced swimming test were also the most severe at the 5 h time point. Ethanol (1.5 g/kg) cotreatment on each administration day, even at non-toxic and/or euphoric doses, enhanced these stressor-like alterations. On the other hand, the protective effects of daily coadministered drugs related to benzodiazepine (5 mg/kg Ro 15-4513), dopamine (0.5 mg/kg SCH 23390), muscarinic (0.25 mg/kg pirenzepine) and serotonin (5 mg/kg ketanserin) receptors could be observed on the number of HSP-immunoreactive (24 h) and SAPK-immunoreactive cells (5 h). Against the stressor-altered swimming behaviors, Ro 15-4513 and SCH 23390 were more effective as compared to pirenzepine and ketanserin.
Hayase
Tamaki
T
Department of Legal Medicine, Faculty of Medicine, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. hayaselab@jweb.co.jp
Yamamoto
Yoshiko
Y
Yamamoto
Keiichi
K
Muso
Eri
E
Shiota
Kohei
K
D000818:Animals; D001386:Azides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004334:Drug Administration Schedule; D000431:Ethanol / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects*; D007263:Infusions, Parenteral; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology; D013550:Swimming
D001386:Azides; D001552:Benzazepines; D002492:Central Nervous System Depressants; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D006360:Heat-Shock Proteins; D018727:Muscarinic Antagonists; D012702:Serotonin Antagonists; D001569:Benzodiazepines; D010890:Pirenzepine; D000431:Ethanol; C042957:Ro 15-4513; D007650:Ketanserin; D020928:Mitogen-Activated Protein Kinases; D003042:Cocaine