Central administration of p-hydroxyamphetamine produces a behavioral stimulant effect in rodents: evidence for the involvement of dopaminergic systems.
OBJECTIVE
It is well-known that amphetamine induces increased locomotor activity in rodents. We previously found that intracerebroventricular (i.c.v.) administration of p-hydroxyamphetamine (p-OHA), an amphetamine metabolite, increases synaptic dopamine (DA) levels in the striatum. In the present study, we investigated the effect of p-OHA on locomotor activity in rodents.


RESULTS
In mice, i.c.v. administration of p-OHA significantly increased locomotor activity in a dose-dependent manner. p-Hydroxynorephedrine, another amphetamine metabolite, did not increase locomotor activity. This effect of p-OHA was inhibited by pretreatment with nomifensine, a dopamine-uptake inhibitor, but not by fluoxetine, a serotonin-uptake inhibitor, or diethyldithiocarbamate, a dopamine-beta-hydroxylase inhibitor. Furthermore, we tested the effects of microinjections of p-OHA into the rat nucleus accumbens (NAc) on locomotor activity. Local infusion of p-OHA into the NAc significantly increased locomotor activity. As in mice, the increased locomotor activity induced by p-OHA microinjection into the NAc in rats was inhibited by nomifensine.


CONCLUSIONS
These data suggest that dopaminergic systems in the NAc may play important roles in p-OHA-induced locomotor activity in rodents.
Onogi
Hiroshi
H
Department of Pharmacology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan.
Hozumi
Masato
M
Nakagawasai
Osamu
O
Arai
Yuichiro
Y
Ishigaki
Seiichiro
S
Sato
Atsushi
A
Furuta
Seiichi
S
Niijima
Fukie
F
Tan-No
Koichi
K
Tadano
Takeshi
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D004050:Ditiocarb / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects* / Q000378:metabolism; D009627:Nomifensine / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors; D010136:p-Hydroxyamphetamine / Q000008:administration & dosage*
D000697:Central Nervous System Stimulants; D004050:Ditiocarb; D004298:Dopamine; D018765:Dopamine Uptake Inhibitors; D004299:Dopamine beta-Hydroxylase; D004791:Enzyme Inhibitors; D005473:Fluoxetine; D009627:Nomifensine; D017367:Selective Serotonin Reuptake Inhibitors; D010136:p-Hydroxyamphetamine