The fall of homovanillic acid and 5-hydroxyindoleacetic acid concentrations in brains of mice withdrawn from repeated morphine treatment and their restoration by acute morphine administration.
The striatal homovanillic acid (HVA) and cerebral 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were estimated in male mice withdrawn from 3- to 5-day morphine treatment (total dose: 1,100-2,350 mg/kg). All mice were given probenecid (200 mg/kg, 2 hours). The HVA concentration was decreased (by 26%) in mice withdrawn from 3-day treatment, but the 5-HIAA concentration fell (by 22%) only after 4-day treatment. An acute morphine dose (30 mg/kg, 2 hours) clearly elevated the HVA concentration in mice withdrawn from 4-day treatment, but mice withdrawn from 3-day treatment tended to be tolerant to the HVA concentration elevating effect of morphine. The acute dose increased the 5-HIAA concentration in mice withdrawn from 4-day treatment, by 20-40%, but the mice withdrawn from 3-day treatment were clearly tolerant to this effect of morphine. These results suggest that endogenous activities of dopaminergic and 5-HTergic neurons are attenuated by repeated morphine treatment. However, such attenuation seems to reactivate these neurons to respond to acute morphine administration nearly normally.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013687:Telencephalon / Q000187:drug effects* / Q000378:metabolism
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D009020:Morphine; D011339:Probenecid; D004298:Dopamine; D006719:Homovanillic Acid