Pharmacological Characteristics of Hyperambulation Induced by the Sigma Ligand (+)-3-PPP in Rats

The Japanese Journal of Pharmacology

Ichiro Hirotsu¹  Tomochika Ohno¹  Makoto Koyama¹  Naomi Honbo¹ 

[1] Laboratory of Experimental Pharmacology, Suntory Institute for Biomedical Research

关键词: Sigma receptor;    (+)-3-PPP ((+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine);    Hyperambulation;    Dopaminergic system;   

DOI  :  10.1254/jjp.65.1

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(25)Cited-By(3)(+)-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 α-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 a-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.

【 授权许可】

Unknown