Chlorpromazine-induced alterations in hypothalamic amine metabolism and stress responses in severe cold.
To investigate the effects on the central nervous system of severe cold stress with and without chlorpromazine, guinea pigs were treated with chlorpromazine or 0.9% NaCl and exposed to -20 degrees C or +23 degrees C for 1 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxy-tryptamine (5-HT), 3-methoxy-4-hydroxyphenyl ethylene glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxy-indoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum, urinary and vitreous fluid catecholamines, muscle and liver glycogen, and blood glucose were also measured. Chlorpromazine caused distinct hypothermia at -20 degrees C and slight hypothermia at +23 degrees C. The rise in hypothalamic MHPG, 5-HIAA and MHPG/NA and in 5-HIAA/5-HT ratios in the cold indicate increased noradrenergic and serotonergic activity. The latter was inhibited by chlorpromazine and a drug-induced inhibition of noradrenergic neurons could not be ruled out. Chlorpromazine increased the turnover of DA at room temperature and the same tendency was seen in the cold. The hypothermic animals had low serum catecholamines, indicating diminished sympathetic activity. The chlorpromazine-treated cold-exposed animals did not react to the environmental stress by sympathetic activation, as urinary NA and adrenaline were not elevated, but DA was excreted by all the drug-treated animals. Vitreous fluid NA and DA were elevated as an indicator of cold stress, and no drug effect was seen in this fluid.
Kortelainen
M L
ML
Department of Forensic Medicine, University of Oulu, Finland.
Lapinlampi
T
T
Hirvonen
J
J
D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D001833:Body Temperature Regulation / Q000187:drug effects*; D002746:Chlorpromazine / Q000633:toxicity*; D003080:Cold Temperature / Q000009:adverse effects*; D004298:Dopamine / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006168:Guinea Pigs; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D009132:Muscles / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D014822:Vitreous Body / Q000187:drug effects
D001786:Blood Glucose; D008112:Liver Glycogen; D018377:Neurotransmitter Agents; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D006003:Glycogen; D002746:Chlorpromazine; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid; D004837:Epinephrine