Pharmacological characteristics of hyperambulation induced by the sigma ligand (+)-3-PPP in rats.
(+)-3-(3-Hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP), a sigma ligand, at doses above 3 mg/kg (s.c.) increased the ambulatory activity of rats, while the (-) isomer of 3-PPP with low affinity for sigma receptors, did not significantly modify the ambulatory activity at 10 and 30 mg/kg (s.c.). The ambulation-increasing effect of (+)-3-PPP was prevented by the sigma receptor antagonists BMY 14802 and rimcazole or the sigma/dopamine D2 antagonist haloperidol. The (+)-3-PPP effect was also attenuated by pretreatment with the monoamine depletor reserpine or the tyrosine hydroxylase inhibitor alpha-methyltyrosine, but was not affected by the tryptophan hydroxylase inhibitor p-chlorophenylalanine. Moreover, the (+)-3-PPP effect was antagonized by the dopamine D2 antagonist sulpiride, whereas pretreatment with the 5-HT1A agonist 8-OH-DPAT and the alpha-adrenoceptor antagonist phenoxybenzamine did not exert any significant effect. These results indicate that sigma receptors are involved in the neuronal mechanism(s) of hyperambulation induced by (+)-3-PPP, and the sigma system may exert both a presynaptic action and a dopamine D2 receptor-mediated action to increase the central dopaminergic function.
Hirotsu
I
I
Laboratory of Experimental Pharmacology, Suntory Institute for Biomedical Research, Osaka, Japan.
Koyama
M
M
Honbo
N
N
Ohno
T
T
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D015259:Dopamine Agents / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010880:Piperidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013237:Stereoisomerism; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D015259:Dopamine Agents; D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D010880:Piperidines; D017480:Receptors, sigma; D017366:Serotonin Receptor Agonists; C026539:preclamol; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase